Półpasiec – Patofizjologia i mechanizm

Półpasiec
Patofizjologia i mechanizm

Półpasiec (herpes zoster) jest wynikiem reaktywacji latentnego wirusa varicella-zoster (VZV) zlokalizowanego w zwojach czuciowych nerwów czaszkowych lub korzeni grzbietowych, najczęściej u osób z obniżoną odpornością komórkową, zwłaszcza po 50. roku życia. Reaktywacja prowadzi do replikacji wirusa w neuronach, transportu aksonalnego do skóry i powstania charakterystycznej pęcherzykowej wysypki w dermatomie unerwianym przez zajęty zwój. Patogeneza obejmuje intensywny stan zapalny, martwicę neuronów oraz uszkodzenia zwojów, co tłumaczy występowanie neuralgii popółpaścowej (PHN). VZV unika odpowiedzi immunologicznej poprzez hamowanie ekspresji MHC klasy I i II oraz indukcję autofagii limfocytów T, co sprzyja reaktywacji i rozprzestrzenianiu się wirusa. Wysokie miana przeciwciał IgG, IgM i IgA pojawiają się szybciej podczas reaktywacji niż w infekcji pierwotnej, jednak kluczową rolę w kontroli infekcji odgrywa odporność komórkowa. Zajęcie OUN może prowadzić do poważnych powikłań, takich jak zapalenie mózgu, porażenia nerwów czaszkowych czy zespół Guillaina-Barrégo. Nowe badania wskazują na rolę małych pęcherzyków zewnątrzkomórkowych (sEVs) przenoszących białko IE62, które tłumi odpowiedź przeciwwirusową komórek, co może ułatwiać rozprzestrzenianie wirusa i powstawanie powikłań, w tym zwiększonego ryzyka udaru mózgu poprzez aktywację płytek krwi i mechanizmy krzepnięcia.

Patogeneza półpaśca

Półpasiec (herpes zoster) jest chorobą wirusową wywołaną przez reaktywację wirusa varicella-zoster (VZV), który pozostaje w stanie uśpienia w zwojach czuciowych nerwów czaszkowych lub zwojach korzeni grzbietowych po wcześniejszym zakażeniu ospą wietrzną (varicella)¹². Wirus VZV należy do rodziny herpeswirusów i jest wysoce specyficzny dla człowieka³⁴. Podczas pierwotnego zakażenia, wirus przedostaje się do czuciowych ciał komórek nerwowych w zwojach poprzez transport aksonalny wsteczny z miejsc replikacji w skórze lub poprzez wiremię z udziałem komórek T⁵.

Mechanizm latencji i reaktywacji

Po zakażeniu pierwotnym VZV pozostaje w stanie latencji w zwojach czuciowych, głównie w zwojach korzeni grzbietowych lub zwojach nerwów czaszkowych⁶⁷. Mechanizm, poprzez który wirus pozostaje w stanie latencji w komórkach nerwowych lub ulega późniejszej reaktywacji, nie jest w pełni poznany⁸⁹. Uważa się, że półpasiec występuje w wyniku niepowodzenia systemu obronnego układu odpornościowego w kontrolowaniu latentnej replikacji wirusa¹⁰.

Czynniki związane ze zwiększonym ryzykiem rozwoju półpaśca obejmują starzenie się, immunosupresję, wewnątrzmaciczną ekspozycję na VZV oraz przebycie ospy wietrznej przed 18 miesiącem życia¹¹. Częstość występowania półpaśca jest silnie skorelowana ze stanem układu odpornościowego – osoby utrzymujące wysoki poziom odporności rzadko rozwijają półpasiec¹².

Molekularne mechanizmy reaktywacji

Podczas reaktywacji, wirus replikuje się w ciałach komórek nerwowych, a wiriony uwalniane z komórek są transportowane wzdłuż nerwu do obszaru skóry unerwianego przez dany zwój¹³¹⁴. W skórze wirus powoduje miejscowy stan zapalny i powstawanie pęcherzyków¹⁵. Ból towarzyszący półpaścowi jest wynikiem zapalenia zajętych nerwów przez wirus¹⁶.

Genom VZV zawiera co najmniej 71 znanych lub przewidywanych ramek odczytu (ORF)¹⁷. Replikacja genomu VZV i ekspresja genów wirusowych zależą od kodowanych przez wirusa i komórkowych czynników transkrypcyjnych oraz komórkowych systemów translacyjnych¹⁸. Białka tegumentu ORF47 i ORF66 są ważnymi kinazami serynowo/treoninowymi, które autofosforylują i fosforylują wirusowe czynniki transkrypcyjne i inne białka VZV¹⁹.

Rola układu odpornościowego w patogenezie półpaśca

Odporność komórkowa odgrywa kluczową rolę w kontroli latencji VZV i ograniczaniu potencjalnej reaktywacji wirusa prowadzącej do półpaśca²⁰. Specyficzna odpowiedź immunologiczna komórkowa przeciwko VZV, która rozwija się podczas ospy wietrznej, jest niezbędna do zakończenia infekcji²¹.

Odpowiedź komórkowa a reaktywacja wirusa

Najbardziej prawdopodobnym mechanizmem reaktywacji VZV jest spadek odporności komórkowej przeciwko wirusowi²². Częstość występowania i ciężkość półpaśca oraz neuralgii popółpaścowej (PHN) wzrasta z wiekiem, co wiąże się ze związanym z wiekiem spadkiem odporności komórkowej na VZV²³. Staje się to szczególnie widoczne po 50 roku życia, gdy ryzyko reaktywacji VZV znacznie wzrasta, praktycznie podwajając się co dekadę²⁴.

Reaktywowany wirus namnaża się i rozprzestrzenia w zwoju, infekując wiele dodatkowych neuronów i komórek podporowych – proces ten powoduje intensywny stan zapalny i martwicę neuronów²⁵. Reaktywacja latentnego VZV powoduje również rozległe uszkodzenia zwoju, co prawdopodobnie wyjaśnia częste występowanie neuralgii popółpaścowej²⁶.

Interakcje wirusowo-komórkowe

VZV wzmacnia infekcję poprzez hamowanie wielu mechanizmów obronnych gospodarza, takich jak zmniejszenie ekspresji głównego kompleksu zgodności tkankowej klasy I (MHC I) i hamowanie genów odpowiedzi na interferon. Umożliwia to wirusowi częściowe uniknięcie odpowiedzi immunologicznej²⁷.

Produkty genowe kodowane przez VZV mogą obniżać ekspresję cząsteczek MHC-I w limfocytach T, zmniejszać wrażliwość limfocytów T na antygeny i zmniejszać funkcję rozpoznawania immunologicznego limfocytów T CD8+²⁸. VZV hamuje ekspresję MHC-I, MHC-II i innych cząsteczek poprzez regulację immunologiczną oraz aktywuje autofagię limfocytów T, co utrudnia rozpoznanie przez układ odpornościowy komórek zakażonych VZV, prowadząc do reaktywacji wirusa²⁹.

Cytokiny i chemokiny w odpowiedzi na VZV

Pojawienie się zmian skórnych w półpaścu zbiega się z nasiloną proliferacją limfocytów T specyficznych dla VZV³⁰. Produkcja interferonu alfa pojawia się wraz z ustępowaniem półpaśca³¹. U pacjentów z prawidłową odpornością, specyficzne przeciwciała (IgG, IgM i IgA) pojawiają się szybciej i osiągają wyższe miana podczas reaktywacji (półpasiec) niż podczas infekcji pierwotnej, powodując długotrwałą, wzmocnioną odporność komórkową na wirus varicella-zoster³²³³.

Proces reaktywacji VZV jest ściśle związany z rozpoznawaniem wirusów przez receptory rozpoznające wzorce, interakcją podtypów limfocytów T i uwalnianiem cytokin³⁴. Badania wykazały, że poziom odporności komórkowej na VZV określa ryzyko i ciężkość półpaśca oraz PHN, podczas gdy przeciwciała przeciwko VZV nie odgrywają klinicznie istotnej roli³⁵.

Patogeneza na poziomie tkanek

Zajęcie dermatologiczne w półpaścu ma charakter dośrodkowy i podąża za dermatomem³⁶. W większości przypadków zajęte są korzenie lędźwiowe i szyjne, natomiast zajęcie ruchowe jest rzadkie³⁷.

Mechanizm uszkodzenia tkanek

Po reaktywacji VZV dochodzi do intensywnej reakcji zapalnej, która obejmuje również opony miękkie; obserwuje się zarówno komórki plazmatyczne, jak i limfocyty³⁸. To zapalenie w zwoju korzenia grzbietowego może być połączone z martwicą krwotoczną komórek nerwowych. Rezultatem jest utrata neuronów i zwłóknienie³⁹.

Zajęcie OUN nie jest rzadkie, ponieważ wirus znajduje się w zwojach korzeni czuciowych, może on wpływać na każdą część mózgu, powodując porażenia nerwów czaszkowych, osłabienie mięśni, porażenie przepony, neurogenną pęcherz moczowy, zespół Guillaina-Barrégo i zapalenie rdzenia kręgowego⁴⁰. W ciężkich przypadkach pacjenci mogą rozwinąć zapalenie mózgu⁴¹.

Transport wirusa w organizmie

Kiedy dochodzi do reaktywacji VZV w zwojach, wirus dociera do skóry poprzez transport aksonalny dośrodkowy, powodując objawy półpaśca, który charakteryzuje się wysypką pęcherzykową w dermatomie unerwionym przez zajęty zwój⁴². Zakażone komórki T transportują wirusa przez krążenie, migrują do skóry i inicjują tworzenie zmian skórnych⁴³. Komórki T dostarczają również VZV do zwojów korzeni grzbietowych (DRG), gdzie ustala się latencja⁴⁴.

Częstość zajęcia dermatologicznego jest skorelowana z centrypetowym rozmieszczeniem pierwotnych zmian ospy wietrznej. Ten wzorzec sugeruje, że latencja może wynikać z ciągłego rozprzestrzeniania się wirusa podczas ospy wietrznej z zakażonych komórek skóry do zakończeń nerwów czuciowych, z późniejszym wstępowaniem do zwojów⁴⁵. Alternatywnie, zwoje mogą zostać zakażone na drodze hematogennej podczas fazy wiremicznej ospy wietrznej, a częstość zajęcia dermatomu w półpaścu może odzwierciedlać zwoje najczęściej narażone na bodźce reaktywujące⁴⁶.

Nowe odkrycia w patogenezie półpaśca

Naukowcy z University of Colorado Anschutz Medical Campus odkryli nową strategię unikania odpowiedzi immunologicznej przez wirus varicella-zoster, która może pozwalać mu wpływać na tkanki odległe od pierwotnego miejsca infekcji⁴⁷⁴⁸.

Nowe mechanizmy rozprzestrzeniania się wirusa

Odkryto, że białko IE62 pakowane wewnątrz małych pęcherzyków zewnątrzkomórkowych (sEVs) może przemieszczać się z miejsca infekcji, gdzie przenika do komórek i wyłącza ich odpowiedź przeciwwirusową, otwierając drzwi do infekcji przez wirusa⁴⁹⁵⁰. To badanie jako pierwsze pokazuje dokładnie, jak wirus wykorzystuje maszynerię sEV zakażonych komórek⁵¹.

Białko to wyłącza odpowiedź przeciwwirusową w komórkach znacznie wcześniej niż dotychczas sądzono⁵². Naukowcy uważają, że białko to prawdopodobnie jest pakowane do sEVs i transportowane wzdłuż neuronów prowadzących do skóry, czyniąc komórki pod skórą podatnymi na pełną infekcję⁵³.

Związek z chorobami współistniejącymi

Mechanizm ten może być odpowiedzialny za powszechne współinfekcje i zdarzenia immunosupresyjne obserwowane klinicznie u osób zakażonych VZV⁵⁴⁵⁵. Ten mechanizm może dostarczyć wskazówek na temat działania innych wirusów i powodowania infekcji⁵⁶.

Nowe badania rozwiązują długotrwałą zagadkę: Dlaczego przejście półpaśca zwiększa ryzyko udaru mózgu?⁵⁷ Małe egzosomy wydają się być mechanizmem odpowiedzialnym za to połączenie. Zawierają one białka zaangażowane w krzepnięcie i aktywację płytek krwi, co z kolei może prowadzić do udarów⁵⁸. Wcześniejsze badania wykazały, że zwiększone ryzyko udaru utrzymuje się do roku po objawach półpaśca, które zwykle trwają kilka tygodni⁵⁹.

Modele badawcze w patogenezie półpaśca

Badanie patogenezy VZV jest wyzwaniem, ponieważ VZV jest wysoce specyficznym dla człowieka wirusem, który ma niewielką zdolność lub nie ma zdolności do zakażania innych gatunków⁶⁰. Do badań wykorzystuje się jednak ksenotransplantaty ludzkich tkanek u myszy z ciężkim złożonym niedoborem odporności (SCID), co umożliwia analizę zakażenia VZV w zróżnicowanych ludzkich komórkach w ich typowym mikrośrodowisku tkankowym⁶¹.

Modele mysie z ksenotransplantatami

W tych modelach odpowiedzi wrodzone, które modulują procesy infekcyjne, mogą być oceniane niezależnie od odporności adaptacyjnej, która jest nieobecna u myszy SCID⁶². VZV przechodzi przejście do stanu przetrwania w neuronach w ksenotransplantatach DRG, podczas gdy postępująca infekcja lityczna występuje w ksenotransplantatach skóry i komórek T, co wskazuje, że wyciszanie genów VZV jest cechą specyficzną dla neuronów⁶³.

Patogeneza VZV zależy od przeprogramowania szlaków sygnałowych komórkowych w zakażonych komórkach, aby wspierać przeżycie komórek i zakłócać wrodzone mechanizmy obronne przeciwwirusowe. Umożliwia to zakażonym komórkom T dotarcie do skóry i DRG, wspiera tworzenie wypełnionych wirusem zmian na powierzchni skóry i ułatwia ustanowienie latencji⁶⁴.

Modele zwierzęce

W rozprawie doktorskiej wykorzystującej model makaka rezusa do badania interakcji gospodarz-patogen w płucach i zwojach czuciowych (miejscach infekcji pierwotnej i latencji), a także roli, jaką odgrywają komórki T w tropizmie i reaktywacji wirusa Simian Varicella Virus (SVV), odkryto, że DNA i transkrypty SVV są wykrywane w zwojach 3 dni po infekcji, przed rozwojem ospy wietrznej⁶⁵.

Co ciekawe, wykazano również, że limfocyty T CD4 i CD8 infiltrują zwoje czuciowe 3 dni po infekcji, przed rozwojem odporności komórkowej, co sugeruje rolę limfocytów T w tropizmie SVV do zwojów⁶⁶. Ostra infekcja SVV zwojów wywołuje silne zmiany w ekspresji genów wskazujące na wrodzoną przeciwwirusową odpowiedź immunologiczną wraz z obniżoną regulacją genów, które odgrywają rolę w funkcjonowaniu układu nerwowego⁶⁷.

Implikacje kliniczne i terapeutyczne

Zrozumienie molekularnych mechanizmów patogenezy półpaśca ma kluczowe znaczenie dla opracowania skutecznych strategii leczenia i zapobiegania.⁶⁸

Znaczenie szczepionki przeciwko półpaścowi

Szczepionka Shingrix różni się znacznie od innych szczepionek, które są wykonane z osłabionej formy wirusa⁶⁹. Jest pierwszą szczepionką przeciwko półpaścowi, która łączy nieżywy antygen ze specjalnie zaprojektowanym adiuwantem⁷⁰. Badania wykazały, że szczepionka stymuluje produkcję specyficznych komórek pamięci immunologicznej (komórki T CD4), które generują silną i trwałą ochronę przed wirusem⁷¹.

Szczepionka HZ/su (Shingrix) łączy główny antygen korzeniowy VZV gE i układ adiuwantów (AS01B)⁷². Systemy adiuwantów są używane do wzmocnienia wrodzonej odpowiedzi przeciwwirusowej i wzmocnienia lub dostosowania odpowiedzi immunologicznej⁷³. gE szczepionki Shingrix jest determinantem antygenowym limfocytów B i CD4+ T pochodzącym z wirusa; jest to najbardziej obfite białko powierzchniowe VZV i odgrywa istotną rolę w replikacji wirusa, stanowiąc potencjalny cel skutecznej odpowiedzi immunologicznej⁷⁴.

Leczenie półpaśca

Terapia przeciwwirusowa przyspiesza ustępowanie zmian, zmniejsza ostry ból i pomaga zapobiegać neuralgii popółpaścowej, szczególnie u pacjentów w podeszłym wieku⁷⁵. Acyklowir 800 mg, pięć razy dziennie przez pięć dni, walacyklowir 1 gram trzy razy dziennie przez pięć dni i famcyklowir 500 mg trzy razy dziennie przez siedem dni to leki przeciwwirusowe stosowane w leczeniu półpaśca⁷⁶.

Powikłania półpaśca obejmują wtórne zakażenie bakteryjne, neuralgię popółpaścową, bliznowacenie, porażenie nerwów i zapalenie mózgu w przypadku półpaśca rozsianego⁷⁷. Leczenie jest najbardziej skuteczne w ciągu 72 godzin od wystąpienia objawów⁷⁸. Te leki przeciwwirusowe przyspieszają ustępowanie zmian, zmniejszają rozwój nowych zmian i shedding wirusa oraz zmniejszają nasilenie ostrego bólu⁷⁹.

Zrozumienie patogenezy półpaśca na poziomie molekularnym i komórkowym jest kluczowe dla opracowania nowych, skuteczniejszych strategii terapeutycznych i profilaktycznych, które mogą pomóc w zmniejszeniu zachorowalności i ciężkości tej powszechnej choroby wirusowej.

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Materiały źródłowe

#1 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
Herpes zoster is commonly known as shingles. It is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the sensory ganglia of the cranial nerve or the dorsal root ganglia after a previous varicella infection. […] It is believed that zoster occurs due to the failure of the immune defense system to control the latent replication of the virus. The incidence of herpes zoster is strongly correlated to the immune status. Individuals who maintain a high level of immunity rarely develop shingles. The infection is not benign and can present in many ways. Even after herpes zoster resolves, many patients continue to suffer from moderate to severe pain known as postherpetic neuralgia. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus. […] Cutaneous lesions of herpes zoster produce Varicella-zoster virus-specific T-cell proliferation, while the production of interferon alfa leads to the resolution of herpes zoster. In immunocompetent patients, specific antibodies (IgG, IgM, and IgA) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection causing long-lasting, enhanced, cell-mediated immunity to the varicella-zoster virus.
#2 Shingles – Wikipedia
https://en.wikipedia.org/wiki/Shingles
Shingles is caused by the varicella zoster virus (VZV) that also causes chickenpox. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence. Once the chickenpox has resolved, the virus can remain dormant (inactive) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters. […] How the virus remains dormant in nerve cells or subsequently re-activates is not well understood. […] The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.
#3 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
Varicella zoster virus (VZV) is the causative agent of varicella (chickenpox) and zoster (shingles). […] Investigating VZV pathogenesis is challenging as VZV is a human-specific virus and infection does not occur, or is highly restricted, in other species. […] However, the use of human tissue xenografts in mice with severe combined immunodeficiency (SCID) enables the analysis of VZV infection in differentiated human cells in their typical tissue microenvironment. […] In this Review, we discuss how these models have improved our understanding of VZV pathogenesis. […] During primary infection, virions presumably gain access to the sensory nerve cell bodies in ganglia by retrograde axonal transport from skin sites of replication or by T cell viraemia, and latent infection is established.
#4 Molecular mechanisms of varicella zoster virus pathogenesis | Nature Reviews Microbiology
https://www.nature.com/articles/nrmicro3215
Varicella zoster virus (VZV) causes varicella and zoster. This herpesvirus is highly human-specific; therefore, human tissue xenografts in mice with severe combined immunodeficiency (SCID) provide an opportunity to define the molecular mechanisms of VZV pathogenesis and tissue tropism. […] VZV-infected T cells transport the virus through the circulation, migrate into skin and initiate cutaneous lesion formation. T cells also deliver VZV to dorsal root ganglia (DRG), where latency is established. […] VZV undergoes a transition to persistence in neurons within DRG xenografts, whereas progressive lytic infection occurs in skin and T cell xenografts, which indicates that VZV gene silencing is a neuron-specific characteristic. […] VZV pathogenesis depends on reprogramming cell signalling pathways within infected cells to support cell survival and disrupt innate antiviral defences. This enables infected T cells to reach skin and DRG, supports the formation of virus-filled lesions at the skin surface and facilitates the establishment of latency.
#5 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
Varicella zoster virus (VZV) is the causative agent of varicella (chickenpox) and zoster (shingles). […] Investigating VZV pathogenesis is challenging as VZV is a human-specific virus and infection does not occur, or is highly restricted, in other species. […] However, the use of human tissue xenografts in mice with severe combined immunodeficiency (SCID) enables the analysis of VZV infection in differentiated human cells in their typical tissue microenvironment. […] In this Review, we discuss how these models have improved our understanding of VZV pathogenesis. […] During primary infection, virions presumably gain access to the sensory nerve cell bodies in ganglia by retrograde axonal transport from skin sites of replication or by T cell viraemia, and latent infection is established.
#6 Shingles – Wikipedia
https://en.wikipedia.org/wiki/Shingles
Shingles is caused by the varicella zoster virus (VZV) that also causes chickenpox. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence. Once the chickenpox has resolved, the virus can remain dormant (inactive) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters. […] How the virus remains dormant in nerve cells or subsequently re-activates is not well understood. […] The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.
#7 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
Herpes zoster is a viral infection that develops when the varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. […] Zoster probably results most often from a failure of the immune system to contain latent VZV replication. […] Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs that also encompasses the leptomeninges; both plasma cells and lymphocytes are noted. This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. […] The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alfa appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulins G, M, and A [IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection.
#8 Shingles – Wikipedia
https://en.wikipedia.org/wiki/Shingles
Shingles is caused by the varicella zoster virus (VZV) that also causes chickenpox. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence. Once the chickenpox has resolved, the virus can remain dormant (inactive) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters. […] How the virus remains dormant in nerve cells or subsequently re-activates is not well understood. […] The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.
#9 Chapter 23: Zoster | Pink Book | CDC
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-23-zoster.html
Herpes zoster is the result of reactivation of latent VZV infection. […] The immunologic mechanism that controls latency of VZV is not well understood. […] However, factors associated with increased risk of developing herpes zoster disease include aging, immunosuppression, intrauterine exposure to VZV, and having had varicella at younger than age 18 months.
#10 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
Herpes zoster is commonly known as shingles. It is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the sensory ganglia of the cranial nerve or the dorsal root ganglia after a previous varicella infection. […] It is believed that zoster occurs due to the failure of the immune defense system to control the latent replication of the virus. The incidence of herpes zoster is strongly correlated to the immune status. Individuals who maintain a high level of immunity rarely develop shingles. The infection is not benign and can present in many ways. Even after herpes zoster resolves, many patients continue to suffer from moderate to severe pain known as postherpetic neuralgia. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus. […] Cutaneous lesions of herpes zoster produce Varicella-zoster virus-specific T-cell proliferation, while the production of interferon alfa leads to the resolution of herpes zoster. In immunocompetent patients, specific antibodies (IgG, IgM, and IgA) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection causing long-lasting, enhanced, cell-mediated immunity to the varicella-zoster virus.
#11 Chapter 23: Zoster | Pink Book | CDC
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-23-zoster.html
Herpes zoster is the result of reactivation of latent VZV infection. […] The immunologic mechanism that controls latency of VZV is not well understood. […] However, factors associated with increased risk of developing herpes zoster disease include aging, immunosuppression, intrauterine exposure to VZV, and having had varicella at younger than age 18 months.
#12 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
Herpes zoster is commonly known as shingles. It is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the sensory ganglia of the cranial nerve or the dorsal root ganglia after a previous varicella infection. […] It is believed that zoster occurs due to the failure of the immune defense system to control the latent replication of the virus. The incidence of herpes zoster is strongly correlated to the immune status. Individuals who maintain a high level of immunity rarely develop shingles. The infection is not benign and can present in many ways. Even after herpes zoster resolves, many patients continue to suffer from moderate to severe pain known as postherpetic neuralgia. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus. […] Cutaneous lesions of herpes zoster produce Varicella-zoster virus-specific T-cell proliferation, while the production of interferon alfa leads to the resolution of herpes zoster. In immunocompetent patients, specific antibodies (IgG, IgM, and IgA) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection causing long-lasting, enhanced, cell-mediated immunity to the varicella-zoster virus.
#13 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
Herpes zoster is commonly known as shingles. It is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the sensory ganglia of the cranial nerve or the dorsal root ganglia after a previous varicella infection. […] It is believed that zoster occurs due to the failure of the immune defense system to control the latent replication of the virus. The incidence of herpes zoster is strongly correlated to the immune status. Individuals who maintain a high level of immunity rarely develop shingles. The infection is not benign and can present in many ways. Even after herpes zoster resolves, many patients continue to suffer from moderate to severe pain known as postherpetic neuralgia. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus. […] Cutaneous lesions of herpes zoster produce Varicella-zoster virus-specific T-cell proliferation, while the production of interferon alfa leads to the resolution of herpes zoster. In immunocompetent patients, specific antibodies (IgG, IgM, and IgA) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection causing long-lasting, enhanced, cell-mediated immunity to the varicella-zoster virus.
#14 Shingles – Wikipedia
https://en.wikipedia.org/wiki/Shingles
Shingles is caused by the varicella zoster virus (VZV) that also causes chickenpox. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence. Once the chickenpox has resolved, the virus can remain dormant (inactive) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters. […] How the virus remains dormant in nerve cells or subsequently re-activates is not well understood. […] The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.
#15 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
Herpes zoster is commonly known as shingles. It is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the sensory ganglia of the cranial nerve or the dorsal root ganglia after a previous varicella infection. […] It is believed that zoster occurs due to the failure of the immune defense system to control the latent replication of the virus. The incidence of herpes zoster is strongly correlated to the immune status. Individuals who maintain a high level of immunity rarely develop shingles. The infection is not benign and can present in many ways. Even after herpes zoster resolves, many patients continue to suffer from moderate to severe pain known as postherpetic neuralgia. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus. […] Cutaneous lesions of herpes zoster produce Varicella-zoster virus-specific T-cell proliferation, while the production of interferon alfa leads to the resolution of herpes zoster. In immunocompetent patients, specific antibodies (IgG, IgM, and IgA) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection causing long-lasting, enhanced, cell-mediated immunity to the varicella-zoster virus.
#16 Shingles – Wikipedia
https://en.wikipedia.org/wiki/Shingles
Shingles is caused by the varicella zoster virus (VZV) that also causes chickenpox. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence. Once the chickenpox has resolved, the virus can remain dormant (inactive) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters. […] How the virus remains dormant in nerve cells or subsequently re-activates is not well understood. […] The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.
#17 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
When viral replication is reactivated, VZV reaches the skin via anterograde axonal transport to cause the symptoms of zoster, which is characterized by a vesicular rash in the dermatome that is innervated by the affected ganglion. […] The VZV genome has at least 71 known or predicted ORFs. […] VZV genome replication and viral gene expression depend on virus-encoded and host cell transcription factors and cellular translation systems. […] Furthermore, the tegument proteins ORF47 and ORF66 are important serine/threonine kinases that autophosphorylate and phosphorylate viral transcription factors and other VZV proteins. […] Investigating VZV pathogenesis is challenging as VZV is a highly human-specific virus that has little or no capacity to infect other species. […] In these models, innate responses that modulate infectious processes can be assessed independently of adaptive immunity, which is absent in SCID mice.
#18 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
When viral replication is reactivated, VZV reaches the skin via anterograde axonal transport to cause the symptoms of zoster, which is characterized by a vesicular rash in the dermatome that is innervated by the affected ganglion. […] The VZV genome has at least 71 known or predicted ORFs. […] VZV genome replication and viral gene expression depend on virus-encoded and host cell transcription factors and cellular translation systems. […] Furthermore, the tegument proteins ORF47 and ORF66 are important serine/threonine kinases that autophosphorylate and phosphorylate viral transcription factors and other VZV proteins. […] Investigating VZV pathogenesis is challenging as VZV is a highly human-specific virus that has little or no capacity to infect other species. […] In these models, innate responses that modulate infectious processes can be assessed independently of adaptive immunity, which is absent in SCID mice.
#19 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
When viral replication is reactivated, VZV reaches the skin via anterograde axonal transport to cause the symptoms of zoster, which is characterized by a vesicular rash in the dermatome that is innervated by the affected ganglion. […] The VZV genome has at least 71 known or predicted ORFs. […] VZV genome replication and viral gene expression depend on virus-encoded and host cell transcription factors and cellular translation systems. […] Furthermore, the tegument proteins ORF47 and ORF66 are important serine/threonine kinases that autophosphorylate and phosphorylate viral transcription factors and other VZV proteins. […] Investigating VZV pathogenesis is challenging as VZV is a highly human-specific virus that has little or no capacity to infect other species. […] In these models, innate responses that modulate infectious processes can be assessed independently of adaptive immunity, which is absent in SCID mice.
#20 Epidemiology, clinical manifestations, and diagnosis of herpes zoster – UpToDate
https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-herpes-zoster/print
Herpes zoster, also known as shingles, results from reactivation of latent VZV that gained access to sensory ganglia during varicella. […] During the initial phase of varicella, varicella-zoster virus (VZV) infects the nasopharyngeal lymphoid tissue of a susceptible person. This results in a viremia consisting of VZV-infected T cells that travel throughout the body. […] VZV enhances infection by inhibiting multiple host defenses, such as downregulation of major histocompatibility complex class I expression and inhibition of interferon response genes. This enables the virus to partially evade the immune response. […] Once the rash develops, cell-free virus, which is present only in skin vesicles, is postulated to infect nerve endings in skin and move retrograde along sensory axons to establish life-long latency in neurons within the regional ganglia. […] VZV-specific cell-mediated immune responses that develop during varicella are required to end the infection. These responses also play a critical role in controlling VZV latency and limiting the potential for reactivation to cause herpes zoster.
#21 Epidemiology, clinical manifestations, and diagnosis of herpes zoster – UpToDate
https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-herpes-zoster/print
Herpes zoster, also known as shingles, results from reactivation of latent VZV that gained access to sensory ganglia during varicella. […] During the initial phase of varicella, varicella-zoster virus (VZV) infects the nasopharyngeal lymphoid tissue of a susceptible person. This results in a viremia consisting of VZV-infected T cells that travel throughout the body. […] VZV enhances infection by inhibiting multiple host defenses, such as downregulation of major histocompatibility complex class I expression and inhibition of interferon response genes. This enables the virus to partially evade the immune response. […] Once the rash develops, cell-free virus, which is present only in skin vesicles, is postulated to infect nerve endings in skin and move retrograde along sensory axons to establish life-long latency in neurons within the regional ganglia. […] VZV-specific cell-mediated immune responses that develop during varicella are required to end the infection. These responses also play a critical role in controlling VZV latency and limiting the potential for reactivation to cause herpes zoster.
#22 Herpes Zoster Pathogenesis and Cell-Mediated Immunity and Immunosenescence
https://www.degruyter.com/document/doi/10.7556/jaoa.2009.20009/html?lang=en
Herpes zoster, or shingles, is a localized disease characterized by unilateral radicular pain and a vesicular rash limited to the area of skin innervated by a single dorsal root or cranial sensory ganglion. […] herpes zoster is caused by reactivation of endogenous VZV that has persisted in latent form within sensory ganglia following an earlier episode of chickenpox. […] The incidence and severity of herpes zoster and PHN increase with age in association with an age-related decline in cell-mediated immunity to VZV. […] This latent VZV eventually reactivates, presumably in a single sensory neuron, to cause herpes zoster. The reactivated virus multiplies and spreads within the ganglion, infecting many additional neurons and supporting cellsâa process that causes intense inflammation and neuronal necrosis.
#23 Herpes Zoster Pathogenesis and Cell-Mediated Immunity and Immunosenescence
https://www.degruyter.com/document/doi/10.7556/jaoa.2009.20009/html?lang=en
Herpes zoster, or shingles, is a localized disease characterized by unilateral radicular pain and a vesicular rash limited to the area of skin innervated by a single dorsal root or cranial sensory ganglion. […] herpes zoster is caused by reactivation of endogenous VZV that has persisted in latent form within sensory ganglia following an earlier episode of chickenpox. […] The incidence and severity of herpes zoster and PHN increase with age in association with an age-related decline in cell-mediated immunity to VZV. […] This latent VZV eventually reactivates, presumably in a single sensory neuron, to cause herpes zoster. The reactivated virus multiplies and spreads within the ganglion, infecting many additional neurons and supporting cellsâa process that causes intense inflammation and neuronal necrosis.
#24
https://medical.gsk.com/en-gb/infectious-diseases/herpes-zoster/epidemiology/incidence/
The risk of VZV reactivation increases considerably with age, roughly doubling each decade after 50 years of age. This is thought to be due to the ageing of the immune system and a decline in virus-specific cell-mediated responses. […] In adults aged 70 years and older, over 50,000 cases of shingles occur each year in England and Wales.
#25 Herpes Zoster Pathogenesis and Cell-Mediated Immunity and Immunosenescence
https://www.degruyter.com/document/doi/10.7556/jaoa.2009.20009/html?lang=en
Herpes zoster, or shingles, is a localized disease characterized by unilateral radicular pain and a vesicular rash limited to the area of skin innervated by a single dorsal root or cranial sensory ganglion. […] herpes zoster is caused by reactivation of endogenous VZV that has persisted in latent form within sensory ganglia following an earlier episode of chickenpox. […] The incidence and severity of herpes zoster and PHN increase with age in association with an age-related decline in cell-mediated immunity to VZV. […] This latent VZV eventually reactivates, presumably in a single sensory neuron, to cause herpes zoster. The reactivated virus multiplies and spreads within the ganglion, infecting many additional neurons and supporting cellsâa process that causes intense inflammation and neuronal necrosis.
#26 Herpes Zoster Pathogenesis and Cell-Mediated Immunity and Immunosenescence
https://www.degruyter.com/document/doi/10.7556/jaoa.2009.20009/html?lang=en
Reactivation of latent VZV also results in extensive damage to the ganglion, which is believed to explain the frequent development of PHN. […] It is clear that the level of CMI to VZV determines the risk and severity of herpes zoster and PHN, whereas antibody to VZV plays no clinically significant role.
#27 Epidemiology, clinical manifestations, and diagnosis of herpes zoster – UpToDate
https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-herpes-zoster/print
Herpes zoster, also known as shingles, results from reactivation of latent VZV that gained access to sensory ganglia during varicella. […] During the initial phase of varicella, varicella-zoster virus (VZV) infects the nasopharyngeal lymphoid tissue of a susceptible person. This results in a viremia consisting of VZV-infected T cells that travel throughout the body. […] VZV enhances infection by inhibiting multiple host defenses, such as downregulation of major histocompatibility complex class I expression and inhibition of interferon response genes. This enables the virus to partially evade the immune response. […] Once the rash develops, cell-free virus, which is present only in skin vesicles, is postulated to infect nerve endings in skin and move retrograde along sensory axons to establish life-long latency in neurons within the regional ganglia. […] VZV-specific cell-mediated immune responses that develop during varicella are required to end the infection. These responses also play a critical role in controlling VZV latency and limiting the potential for reactivation to cause herpes zoster.
#28 Research Progress on the Immune Mechanism of Varicella-Zoster Virus – Creative Diagnostics
https://www.creative-diagnostics.com/blog/index.php/research-progress-on-the-immune-mechanism-of-varicella-zoster-virus/
In the primary infection, VZV infection causes T cells to transform into memory T cells, which participate in the transport and transmission of the virus and reduce immune function. […] The gene products encoded by VZV can downregulate the expression of MHC-I molecules in T lymphocytes, reduce the sensitivity of T lymphocytes to antigens, and reduce the immune recognition function of CD8+ T lymphocytes. […] VZV inhibits the expression of MHC-I, MHC-II and other molecules through immune regulation, and activates T lymphocyte autophagy, making it difficult for target cells infected with VZV to be recognized by the immune system, and VZV will be reactivated. […] The process of VZV reactivation is closely related to the recognition of viruses by pattern recognition receptors, the interaction of T lymphocyte subsets and the release of cytokines.
#29 Research Progress on the Immune Mechanism of Varicella-Zoster Virus – Creative Diagnostics
https://www.creative-diagnostics.com/blog/index.php/research-progress-on-the-immune-mechanism-of-varicella-zoster-virus/
In the primary infection, VZV infection causes T cells to transform into memory T cells, which participate in the transport and transmission of the virus and reduce immune function. […] The gene products encoded by VZV can downregulate the expression of MHC-I molecules in T lymphocytes, reduce the sensitivity of T lymphocytes to antigens, and reduce the immune recognition function of CD8+ T lymphocytes. […] VZV inhibits the expression of MHC-I, MHC-II and other molecules through immune regulation, and activates T lymphocyte autophagy, making it difficult for target cells infected with VZV to be recognized by the immune system, and VZV will be reactivated. […] The process of VZV reactivation is closely related to the recognition of viruses by pattern recognition receptors, the interaction of T lymphocyte subsets and the release of cytokines.
#30 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
Herpes zoster is a viral infection that develops when the varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. […] Zoster probably results most often from a failure of the immune system to contain latent VZV replication. […] Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs that also encompasses the leptomeninges; both plasma cells and lymphocytes are noted. This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. […] The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alfa appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulins G, M, and A [IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection.
#31 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
Herpes zoster is a viral infection that develops when the varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. […] Zoster probably results most often from a failure of the immune system to contain latent VZV replication. […] Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs that also encompasses the leptomeninges; both plasma cells and lymphocytes are noted. This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. […] The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alfa appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulins G, M, and A [IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection.
#32 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
Herpes zoster is commonly known as shingles. It is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the sensory ganglia of the cranial nerve or the dorsal root ganglia after a previous varicella infection. […] It is believed that zoster occurs due to the failure of the immune defense system to control the latent replication of the virus. The incidence of herpes zoster is strongly correlated to the immune status. Individuals who maintain a high level of immunity rarely develop shingles. The infection is not benign and can present in many ways. Even after herpes zoster resolves, many patients continue to suffer from moderate to severe pain known as postherpetic neuralgia. […] Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus. […] Cutaneous lesions of herpes zoster produce Varicella-zoster virus-specific T-cell proliferation, while the production of interferon alfa leads to the resolution of herpes zoster. In immunocompetent patients, specific antibodies (IgG, IgM, and IgA) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection causing long-lasting, enhanced, cell-mediated immunity to the varicella-zoster virus.
#33 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
Herpes zoster is a viral infection that develops when the varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. […] Zoster probably results most often from a failure of the immune system to contain latent VZV replication. […] Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs that also encompasses the leptomeninges; both plasma cells and lymphocytes are noted. This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. […] The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alfa appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulins G, M, and A [IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection.
#34 Research Progress on the Immune Mechanism of Varicella-Zoster Virus – Creative Diagnostics
https://www.creative-diagnostics.com/blog/index.php/research-progress-on-the-immune-mechanism-of-varicella-zoster-virus/
In the primary infection, VZV infection causes T cells to transform into memory T cells, which participate in the transport and transmission of the virus and reduce immune function. […] The gene products encoded by VZV can downregulate the expression of MHC-I molecules in T lymphocytes, reduce the sensitivity of T lymphocytes to antigens, and reduce the immune recognition function of CD8+ T lymphocytes. […] VZV inhibits the expression of MHC-I, MHC-II and other molecules through immune regulation, and activates T lymphocyte autophagy, making it difficult for target cells infected with VZV to be recognized by the immune system, and VZV will be reactivated. […] The process of VZV reactivation is closely related to the recognition of viruses by pattern recognition receptors, the interaction of T lymphocyte subsets and the release of cytokines.
#35 Herpes Zoster Pathogenesis and Cell-Mediated Immunity and Immunosenescence
https://www.degruyter.com/document/doi/10.7556/jaoa.2009.20009/html?lang=en
Reactivation of latent VZV also results in extensive damage to the ganglion, which is believed to explain the frequent development of PHN. […] It is clear that the level of CMI to VZV determines the risk and severity of herpes zoster and PHN, whereas antibody to VZV plays no clinically significant role.
#36 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#37 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#38 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
Herpes zoster is a viral infection that develops when the varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. […] Zoster probably results most often from a failure of the immune system to contain latent VZV replication. […] Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs that also encompasses the leptomeninges; both plasma cells and lymphocytes are noted. This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. […] The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alfa appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulins G, M, and A [IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection.
#39 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
Herpes zoster is a viral infection that develops when the varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. […] Zoster probably results most often from a failure of the immune system to contain latent VZV replication. […] Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs that also encompasses the leptomeninges; both plasma cells and lymphocytes are noted. This inflammation in the dorsal root ganglion can be accompanied by hemorrhagic necrosis of nerve cells. The result is neuronal loss and fibrosis. […] The appearance of the cutaneous rash due to herpes zoster coincides with a profound VZV-specific T-cell proliferation. Production of interferon alfa appears with the resolution of herpes zoster. In immunocompetent patients, specific antibodies (immunoglobulins G, M, and A [IgG, IgM, and IgA]) appear more rapidly and reach higher titers during reactivation (herpes zoster) than during the primary infection.
#40 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#41 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#42 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
When viral replication is reactivated, VZV reaches the skin via anterograde axonal transport to cause the symptoms of zoster, which is characterized by a vesicular rash in the dermatome that is innervated by the affected ganglion. […] The VZV genome has at least 71 known or predicted ORFs. […] VZV genome replication and viral gene expression depend on virus-encoded and host cell transcription factors and cellular translation systems. […] Furthermore, the tegument proteins ORF47 and ORF66 are important serine/threonine kinases that autophosphorylate and phosphorylate viral transcription factors and other VZV proteins. […] Investigating VZV pathogenesis is challenging as VZV is a highly human-specific virus that has little or no capacity to infect other species. […] In these models, innate responses that modulate infectious processes can be assessed independently of adaptive immunity, which is absent in SCID mice.
#43 Molecular mechanisms of varicella zoster virus pathogenesis | Nature Reviews Microbiology
https://www.nature.com/articles/nrmicro3215
Varicella zoster virus (VZV) causes varicella and zoster. This herpesvirus is highly human-specific; therefore, human tissue xenografts in mice with severe combined immunodeficiency (SCID) provide an opportunity to define the molecular mechanisms of VZV pathogenesis and tissue tropism. […] VZV-infected T cells transport the virus through the circulation, migrate into skin and initiate cutaneous lesion formation. T cells also deliver VZV to dorsal root ganglia (DRG), where latency is established. […] VZV undergoes a transition to persistence in neurons within DRG xenografts, whereas progressive lytic infection occurs in skin and T cell xenografts, which indicates that VZV gene silencing is a neuron-specific characteristic. […] VZV pathogenesis depends on reprogramming cell signalling pathways within infected cells to support cell survival and disrupt innate antiviral defences. This enables infected T cells to reach skin and DRG, supports the formation of virus-filled lesions at the skin surface and facilitates the establishment of latency.
#44 Molecular mechanisms of varicella zoster virus pathogenesis | Nature Reviews Microbiology
https://www.nature.com/articles/nrmicro3215
Varicella zoster virus (VZV) causes varicella and zoster. This herpesvirus is highly human-specific; therefore, human tissue xenografts in mice with severe combined immunodeficiency (SCID) provide an opportunity to define the molecular mechanisms of VZV pathogenesis and tissue tropism. […] VZV-infected T cells transport the virus through the circulation, migrate into skin and initiate cutaneous lesion formation. T cells also deliver VZV to dorsal root ganglia (DRG), where latency is established. […] VZV undergoes a transition to persistence in neurons within DRG xenografts, whereas progressive lytic infection occurs in skin and T cell xenografts, which indicates that VZV gene silencing is a neuron-specific characteristic. […] VZV pathogenesis depends on reprogramming cell signalling pathways within infected cells to support cell survival and disrupt innate antiviral defences. This enables infected T cells to reach skin and DRG, supports the formation of virus-filled lesions at the skin surface and facilitates the establishment of latency.
#45 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
This infection is contagious to persons with no previous immunity to VZV. However, it is estimated to be only one third as contagious as primary varicella. It is transmitted either via direct contact with the lesions or via the respiratory route. […] The frequency of dermatologic involvement is correlated with the centripetal distribution of the initial varicella lesions. This pattern suggests that the latency may arise from contiguous spread of the virus during varicella from infected skin cells to sensory nerve endings, with subsequent ascent to the ganglia. Alternatively, the ganglia may become infected hematogenously during the viremic phase of varicella, and the frequency of the dermatome involvement in herpes zoster may reflect the ganglia most often exposed to reactivating stimuli.
#46 Herpes Zoster: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/1132465-overview
This infection is contagious to persons with no previous immunity to VZV. However, it is estimated to be only one third as contagious as primary varicella. It is transmitted either via direct contact with the lesions or via the respiratory route. […] The frequency of dermatologic involvement is correlated with the centripetal distribution of the initial varicella lesions. This pattern suggests that the latency may arise from contiguous spread of the virus during varicella from infected skin cells to sensory nerve endings, with subsequent ascent to the ganglia. Alternatively, the ganglia may become infected hematogenously during the viremic phase of varicella, and the frequency of the dermatome involvement in herpes zoster may reflect the ganglia most often exposed to reactivating stimuli.
#47 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
Scientists at the University of Colorado Anschutz Medical Campus have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] These vesicles shut down the immune response. […] The protein shuts down the anti-viral response in the cells far sooner than previously known. […] We believe this protein is likely being packaged into sEVs and shuttled down the neurons that go to your skin, making the cells under the skin vulnerable to the whole infection.
#48 Scientists identify key protein behind spread of shingles virus | ScienceDaily
https://www.sciencedaily.com/releases/2024/07/240725154721.htm
Scientists have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] „This is the first time a clear mechanism has been found that actually ties this virus to an avenue by which it can affect distal organs, far from the site of infection,” said the study’s first author, Christy Niemeyer, PhD, assistant professor of neurology at the University of Colorado School of Medicine.
#49 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
Scientists at the University of Colorado Anschutz Medical Campus have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] These vesicles shut down the immune response. […] The protein shuts down the anti-viral response in the cells far sooner than previously known. […] We believe this protein is likely being packaged into sEVs and shuttled down the neurons that go to your skin, making the cells under the skin vulnerable to the whole infection.
#50 Scientists identify key protein behind spread of shingles virus | ScienceDaily
https://www.sciencedaily.com/releases/2024/07/240725154721.htm
Scientists have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] „This is the first time a clear mechanism has been found that actually ties this virus to an avenue by which it can affect distal organs, far from the site of infection,” said the study’s first author, Christy Niemeyer, PhD, assistant professor of neurology at the University of Colorado School of Medicine.
#51 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
Scientists at the University of Colorado Anschutz Medical Campus have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] These vesicles shut down the immune response. […] The protein shuts down the anti-viral response in the cells far sooner than previously known. […] We believe this protein is likely being packaged into sEVs and shuttled down the neurons that go to your skin, making the cells under the skin vulnerable to the whole infection.
#52 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
Scientists at the University of Colorado Anschutz Medical Campus have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] These vesicles shut down the immune response. […] The protein shuts down the anti-viral response in the cells far sooner than previously known. […] We believe this protein is likely being packaged into sEVs and shuttled down the neurons that go to your skin, making the cells under the skin vulnerable to the whole infection.
#53 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
Scientists at the University of Colorado Anschutz Medical Campus have discovered a new evasion strategy used by the varicella zoster virus, which causes chickenpox and shingles, that may allow it to affect tissues far from the original site of infection. […] They discovered that IE62 packaged inside sEVs can travel from the site of infection, where it penetrates cells and shuts down their antiviral response, opening the door to infection by the virus. […] This study is the first to show exactly how it does this by exploiting the infected cells sEV machinery. […] These vesicles shut down the immune response. […] The protein shuts down the anti-viral response in the cells far sooner than previously known. […] We believe this protein is likely being packaged into sEVs and shuttled down the neurons that go to your skin, making the cells under the skin vulnerable to the whole infection.
#54 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
This mechanism may be responsible for the prevalent co-infections and immunosuppressive events seen clinically in those infected with VZV. […] This mechanism can offer us clues into how other viruses work and cause infection. […] We need to better understand their role in viral spread and secondary disease development to reduce the systemic complications caused by VZV infections.
#55 Scientists identify key protein behind spread of shingles virus | ScienceDaily
https://www.sciencedaily.com/releases/2024/07/240725154721.htm
Bubak said this mechanism may be responsible for the prevalent co-infections and immunosuppressive events seen clinically in those infected with VZV. […] „We need to better understand their role in viral spread and secondary disease development to reduce the systemic complications caused by VZV infections,” she said.
#56 Scientists Identify Key Protein Behind Spread of Shingles Virus
https://news.cuanschutz.edu/news-stories/scientists-identify-key-protein-behind-spread-of-shingles-virus
This mechanism may be responsible for the prevalent co-infections and immunosuppressive events seen clinically in those infected with VZV. […] This mechanism can offer us clues into how other viruses work and cause infection. […] We need to better understand their role in viral spread and secondary disease development to reduce the systemic complications caused by VZV infections.
#57 Shingles and stroke: How can one lead to the other?
https://www.medicalnewstoday.com/articles/mystery-solved-how-shingles-can-increase-stroke-risk
A new study solves a long-standing riddle: Why does getting shingles increase the risk of stroke? […] Tiny exosomes appear to be the mechanism behind the connection. They contain proteins involved in clotting and the activation of platelets, which, in turn can result in strokes. […] A new study identifies the mechanism linking shingles and stroke: prothrombotic and proinflammatory exosomes. […] Previous studies have shown that an increased risk of stroke lasts for up to 1 year after shingles symptoms that typically last a few weeks. The current study shows how that increased risk occurs. […] Cells release exosomes into the bloodstream and other body fluids, allowing them to travel to other places in the body. They aid intracellular communication as they carry their contents from one cell to another.
#58 Shingles and stroke: How can one lead to the other?
https://www.medicalnewstoday.com/articles/mystery-solved-how-shingles-can-increase-stroke-risk
A new study solves a long-standing riddle: Why does getting shingles increase the risk of stroke? […] Tiny exosomes appear to be the mechanism behind the connection. They contain proteins involved in clotting and the activation of platelets, which, in turn can result in strokes. […] A new study identifies the mechanism linking shingles and stroke: prothrombotic and proinflammatory exosomes. […] Previous studies have shown that an increased risk of stroke lasts for up to 1 year after shingles symptoms that typically last a few weeks. The current study shows how that increased risk occurs. […] Cells release exosomes into the bloodstream and other body fluids, allowing them to travel to other places in the body. They aid intracellular communication as they carry their contents from one cell to another.
#59 Shingles and stroke: How can one lead to the other?
https://www.medicalnewstoday.com/articles/mystery-solved-how-shingles-can-increase-stroke-risk
A new study solves a long-standing riddle: Why does getting shingles increase the risk of stroke? […] Tiny exosomes appear to be the mechanism behind the connection. They contain proteins involved in clotting and the activation of platelets, which, in turn can result in strokes. […] A new study identifies the mechanism linking shingles and stroke: prothrombotic and proinflammatory exosomes. […] Previous studies have shown that an increased risk of stroke lasts for up to 1 year after shingles symptoms that typically last a few weeks. The current study shows how that increased risk occurs. […] Cells release exosomes into the bloodstream and other body fluids, allowing them to travel to other places in the body. They aid intracellular communication as they carry their contents from one cell to another.
#60 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
When viral replication is reactivated, VZV reaches the skin via anterograde axonal transport to cause the symptoms of zoster, which is characterized by a vesicular rash in the dermatome that is innervated by the affected ganglion. […] The VZV genome has at least 71 known or predicted ORFs. […] VZV genome replication and viral gene expression depend on virus-encoded and host cell transcription factors and cellular translation systems. […] Furthermore, the tegument proteins ORF47 and ORF66 are important serine/threonine kinases that autophosphorylate and phosphorylate viral transcription factors and other VZV proteins. […] Investigating VZV pathogenesis is challenging as VZV is a highly human-specific virus that has little or no capacity to infect other species. […] In these models, innate responses that modulate infectious processes can be assessed independently of adaptive immunity, which is absent in SCID mice.
#61 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
Varicella zoster virus (VZV) is the causative agent of varicella (chickenpox) and zoster (shingles). […] Investigating VZV pathogenesis is challenging as VZV is a human-specific virus and infection does not occur, or is highly restricted, in other species. […] However, the use of human tissue xenografts in mice with severe combined immunodeficiency (SCID) enables the analysis of VZV infection in differentiated human cells in their typical tissue microenvironment. […] In this Review, we discuss how these models have improved our understanding of VZV pathogenesis. […] During primary infection, virions presumably gain access to the sensory nerve cell bodies in ganglia by retrograde axonal transport from skin sites of replication or by T cell viraemia, and latent infection is established.
#62 Molecular mechanisms of varicella zoster virus pathogenesis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4066823/
When viral replication is reactivated, VZV reaches the skin via anterograde axonal transport to cause the symptoms of zoster, which is characterized by a vesicular rash in the dermatome that is innervated by the affected ganglion. […] The VZV genome has at least 71 known or predicted ORFs. […] VZV genome replication and viral gene expression depend on virus-encoded and host cell transcription factors and cellular translation systems. […] Furthermore, the tegument proteins ORF47 and ORF66 are important serine/threonine kinases that autophosphorylate and phosphorylate viral transcription factors and other VZV proteins. […] Investigating VZV pathogenesis is challenging as VZV is a highly human-specific virus that has little or no capacity to infect other species. […] In these models, innate responses that modulate infectious processes can be assessed independently of adaptive immunity, which is absent in SCID mice.
#63 Molecular mechanisms of varicella zoster virus pathogenesis | Nature Reviews Microbiology
https://www.nature.com/articles/nrmicro3215
Varicella zoster virus (VZV) causes varicella and zoster. This herpesvirus is highly human-specific; therefore, human tissue xenografts in mice with severe combined immunodeficiency (SCID) provide an opportunity to define the molecular mechanisms of VZV pathogenesis and tissue tropism. […] VZV-infected T cells transport the virus through the circulation, migrate into skin and initiate cutaneous lesion formation. T cells also deliver VZV to dorsal root ganglia (DRG), where latency is established. […] VZV undergoes a transition to persistence in neurons within DRG xenografts, whereas progressive lytic infection occurs in skin and T cell xenografts, which indicates that VZV gene silencing is a neuron-specific characteristic. […] VZV pathogenesis depends on reprogramming cell signalling pathways within infected cells to support cell survival and disrupt innate antiviral defences. This enables infected T cells to reach skin and DRG, supports the formation of virus-filled lesions at the skin surface and facilitates the establishment of latency.
#64 Molecular mechanisms of varicella zoster virus pathogenesis | Nature Reviews Microbiology
https://www.nature.com/articles/nrmicro3215
Varicella zoster virus (VZV) causes varicella and zoster. This herpesvirus is highly human-specific; therefore, human tissue xenografts in mice with severe combined immunodeficiency (SCID) provide an opportunity to define the molecular mechanisms of VZV pathogenesis and tissue tropism. […] VZV-infected T cells transport the virus through the circulation, migrate into skin and initiate cutaneous lesion formation. T cells also deliver VZV to dorsal root ganglia (DRG), where latency is established. […] VZV undergoes a transition to persistence in neurons within DRG xenografts, whereas progressive lytic infection occurs in skin and T cell xenografts, which indicates that VZV gene silencing is a neuron-specific characteristic. […] VZV pathogenesis depends on reprogramming cell signalling pathways within infected cells to support cell survival and disrupt innate antiviral defences. This enables infected T cells to reach skin and DRG, supports the formation of virus-filled lesions at the skin surface and facilitates the establishment of latency.
#65 Uncovering Mechanisms of Varicella Zoster Virus Pathogenesis Using a Rhesus Macaque Model
https://escholarship.org/uc/item/7nq6c1jt
Varicella Zoster Virus is neurotropic alpha herpesvirus that causes varicella (chickenpox) and establishes latency in the sensory ganglia. Reactivation results in herpes zoster (HZ, shingles), a painful and debilitating disease that affects 1 million people in the US each year. […] In this dissertation, we use this animal model to investigate the host-pathogen interactions in the lung and sensory ganglia (sites of primary infection and latency) as well as the role that T cells play in SVV tropism and reactivation. […] First, we show that SVV infection causes severe lung damage characterized initially by significant immune infiltration, an up-regulation of genes involved in antiviral immunity and a down-regulation of genes involved in lung development. […] Next, we show that SVV DNA and transcripts are detected in the ganglia 3 days post-infection (DPI), before the development of varicella.
#66 Uncovering Mechanisms of Varicella Zoster Virus Pathogenesis Using a Rhesus Macaque Model
https://escholarship.org/uc/item/7nq6c1jt
Interestingly, CD4 and CD8 T cells were also shown to infiltrate the sensory ganglia 3 DPI; before the development of cell mediated immunity, which suggests a role for T cells in SVV tropism into the ganglia. […] SVV acute infection of the ganglia induces robust gene expression changes indicative of an innate antiviral immune response along with a down-regulation of genes that play a role in the nervous system function. […] Interestingly, genes important for neuron development remained down-regulated 100 days post infection suggesting that SVV latency leads to a long-lived remodeling of the ganglia transcriptional profile. […] This analysis revealed that SVV alters expression of several genes that may support viral replication and dissemination. […] Lastly, we report that the decline of both CD4 and CD8 T cell immunity followed by stress can lead to SVV reactivation, which also causes long-lasting gene expression changes in the ganglia transcriptome, indicative of neuronal damage. These findings provide novel insights into the host pathogen interactions of VZV during acute infection and guide efforts toward more efficacious vaccines and therapeutics.
#67 Uncovering Mechanisms of Varicella Zoster Virus Pathogenesis Using a Rhesus Macaque Model
https://escholarship.org/uc/item/7nq6c1jt
Interestingly, CD4 and CD8 T cells were also shown to infiltrate the sensory ganglia 3 DPI; before the development of cell mediated immunity, which suggests a role for T cells in SVV tropism into the ganglia. […] SVV acute infection of the ganglia induces robust gene expression changes indicative of an innate antiviral immune response along with a down-regulation of genes that play a role in the nervous system function. […] Interestingly, genes important for neuron development remained down-regulated 100 days post infection suggesting that SVV latency leads to a long-lived remodeling of the ganglia transcriptional profile. […] This analysis revealed that SVV alters expression of several genes that may support viral replication and dissemination. […] Lastly, we report that the decline of both CD4 and CD8 T cell immunity followed by stress can lead to SVV reactivation, which also causes long-lasting gene expression changes in the ganglia transcriptome, indicative of neuronal damage. These findings provide novel insights into the host pathogen interactions of VZV during acute infection and guide efforts toward more efficacious vaccines and therapeutics.
#68 The Biology of Varicella-Zoster Virus Replication in the Skin
https://www.mdpi.com/1999-4915/14/5/982
In fibroblasts and MeWo cells, it has been observed that VZV virions localize in single membranes vesicles, presumably amphisomes. […] The major innate immunity cells involved in the reaction to VZV infection, including DCs, Langerhans and NK cells, have been recently reviewed. […] In studies of VZV-infected skin in the SCID-hu mouse model, it was shown that VZV averts the degradation of inhibitor of NF-ÎºBÎ± (IÎºBÎ±) and NF-ÎºB is segregated in the cytoplasm of infected cells. […] Concomitantly, infected keratinocytes also display activation of STAT3 (and therefore increase levels of pSTAT3) which in turn up-regulates the expression of survivin, which blocks host cellsâ apoptosis, thereby guaranteeing the virus survival in the host cell. […] Understanding the molecular mechanisms causing attenuation in skin of the existing VZV vaccine will shed light on pivotal events of VZV skin replication that could be targeted by new antiviral drugs, as well as pave the way for the generation of novel vaccines that could be directed to a wider number of recipients, including immunocompromised children.
#69 Study Reveals How Shingrix Vaccine Works
https://www.drugtopics.com/view/study-reveals-how-shingrix-vaccine-works
Shingrix differs significantly from other vaccines that are made from a weakened form of a virus. […] It is the first shingles vaccine to combine a non-live antigen with a specifically designed adjuvant. […] The study concludes that the vaccine stimulates production of a specific immune memory cell (CD4 T cells) that generates a strong and sustained protection against the virus. […] The research found that Shingrix stimulates the immune system to produce more antibodies and generates a 24-fold increase in T cells over Zostavax. […] Shingrix’s efficacy is approximately 90% for all age groups, even for individuals over age 70. […] We are now measuring the efficacy of the vaccine over the next 10 years and are very optimistic about the results. […] Shingles vaccination can protect against infection and complications.
#70 Study Reveals How Shingrix Vaccine Works
https://www.drugtopics.com/view/study-reveals-how-shingrix-vaccine-works
Shingrix differs significantly from other vaccines that are made from a weakened form of a virus. […] It is the first shingles vaccine to combine a non-live antigen with a specifically designed adjuvant. […] The study concludes that the vaccine stimulates production of a specific immune memory cell (CD4 T cells) that generates a strong and sustained protection against the virus. […] The research found that Shingrix stimulates the immune system to produce more antibodies and generates a 24-fold increase in T cells over Zostavax. […] Shingrix’s efficacy is approximately 90% for all age groups, even for individuals over age 70. […] We are now measuring the efficacy of the vaccine over the next 10 years and are very optimistic about the results. […] Shingles vaccination can protect against infection and complications.
#71 Study Reveals How Shingrix Vaccine Works
https://www.drugtopics.com/view/study-reveals-how-shingrix-vaccine-works
Shingrix differs significantly from other vaccines that are made from a weakened form of a virus. […] It is the first shingles vaccine to combine a non-live antigen with a specifically designed adjuvant. […] The study concludes that the vaccine stimulates production of a specific immune memory cell (CD4 T cells) that generates a strong and sustained protection against the virus. […] The research found that Shingrix stimulates the immune system to produce more antibodies and generates a 24-fold increase in T cells over Zostavax. […] Shingrix’s efficacy is approximately 90% for all age groups, even for individuals over age 70. […] We are now measuring the efficacy of the vaccine over the next 10 years and are very optimistic about the results. […] Shingles vaccination can protect against infection and complications.
#72
https://journals.lww.com/ijdv/fulltext/2024/12000/the_mechanism,_impact,_and_effectiveness_of_herpes.8.aspx
The leading cause of Latent VZV reactivation is an age-associated decrease in CMI. However, CMI can also be decreased by other risk factors such as cell-mediated immune impairment, DM, female sex, genetic inclination, trauma, recent mental pressure, and Caucasian ethnicity. CD4+ and CD8+ T cells seem to be involved in VZV activation. The recombinant subunit vaccine HZ/su is a substitute for a live-attenuated vaccine and is preferable for seriously immunocompromised people as it avoids the risk of complications. The HZ/su vaccine combines the major root antigen VZV gE and an adjuvant system (AS01B). Adjuvant systems are used to invigorate the innate antiviral response and raise or adjust the immune response. The gE of the Shingrix vaccine is a B cell and CD4+ T cell antigenic determinant that is derived from the virus; it is the most abundant surface protein of the VZV and plays an essential role in virus duplication. Hence, it constitutes a potential target for an effective immune response. The AS01 adjuvant system in the Shingrix vaccine is composed of liposomes, 3-O-desacyl-4-monophosphoryl lipid A (MPL), and Quillaja saponaria Molina, fraction 21 (QS21) and helps to improve the activation of the immune system, leading to a potent and maintained immune response. Both components of the Shingrix vaccine (the gE antigen and AS01B adjuvant system) improve the VZV-specific immune response and assist in overcoming the age-associated decrease in immunity that is the dominant driver of shingles.
#73
https://journals.lww.com/ijdv/fulltext/2024/12000/the_mechanism,_impact,_and_effectiveness_of_herpes.8.aspx
The leading cause of Latent VZV reactivation is an age-associated decrease in CMI. However, CMI can also be decreased by other risk factors such as cell-mediated immune impairment, DM, female sex, genetic inclination, trauma, recent mental pressure, and Caucasian ethnicity. CD4+ and CD8+ T cells seem to be involved in VZV activation. The recombinant subunit vaccine HZ/su is a substitute for a live-attenuated vaccine and is preferable for seriously immunocompromised people as it avoids the risk of complications. The HZ/su vaccine combines the major root antigen VZV gE and an adjuvant system (AS01B). Adjuvant systems are used to invigorate the innate antiviral response and raise or adjust the immune response. The gE of the Shingrix vaccine is a B cell and CD4+ T cell antigenic determinant that is derived from the virus; it is the most abundant surface protein of the VZV and plays an essential role in virus duplication. Hence, it constitutes a potential target for an effective immune response. The AS01 adjuvant system in the Shingrix vaccine is composed of liposomes, 3-O-desacyl-4-monophosphoryl lipid A (MPL), and Quillaja saponaria Molina, fraction 21 (QS21) and helps to improve the activation of the immune system, leading to a potent and maintained immune response. Both components of the Shingrix vaccine (the gE antigen and AS01B adjuvant system) improve the VZV-specific immune response and assist in overcoming the age-associated decrease in immunity that is the dominant driver of shingles.
#74
https://journals.lww.com/ijdv/fulltext/2024/12000/the_mechanism,_impact,_and_effectiveness_of_herpes.8.aspx
The leading cause of Latent VZV reactivation is an age-associated decrease in CMI. However, CMI can also be decreased by other risk factors such as cell-mediated immune impairment, DM, female sex, genetic inclination, trauma, recent mental pressure, and Caucasian ethnicity. CD4+ and CD8+ T cells seem to be involved in VZV activation. The recombinant subunit vaccine HZ/su is a substitute for a live-attenuated vaccine and is preferable for seriously immunocompromised people as it avoids the risk of complications. The HZ/su vaccine combines the major root antigen VZV gE and an adjuvant system (AS01B). Adjuvant systems are used to invigorate the innate antiviral response and raise or adjust the immune response. The gE of the Shingrix vaccine is a B cell and CD4+ T cell antigenic determinant that is derived from the virus; it is the most abundant surface protein of the VZV and plays an essential role in virus duplication. Hence, it constitutes a potential target for an effective immune response. The AS01 adjuvant system in the Shingrix vaccine is composed of liposomes, 3-O-desacyl-4-monophosphoryl lipid A (MPL), and Quillaja saponaria Molina, fraction 21 (QS21) and helps to improve the activation of the immune system, leading to a potent and maintained immune response. Both components of the Shingrix vaccine (the gE antigen and AS01B adjuvant system) improve the VZV-specific immune response and assist in overcoming the age-associated decrease in immunity that is the dominant driver of shingles.
#75 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#76 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#77 Herpes Zoster – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441824/
The dermatological involvement is centripetal and follows a dermatome. In most cases, it is the lumbar and cervical roots that are involved, whereas motor involvement is rare. The infection is contagious to individuals who have no prior immunity to varicella-zoster, however, the rates of transmission are low. The virus can be transmitted either via direct skin contact or by inhaling infected droplets. […] The involvement of the CNS is not uncommon. since the virus resides in the sensory root ganglia, it can affect any part of the brain causing cranial nerve palsies, muscular weakness, diaphragmatic paralysis, neurogenic bladder, Guillain Barre syndrome, and myelitis. In severe cases, patients may develop encephalitis. […] Complications of herpes zoster include secondary bacterial infection, post-herpetic neuralgia, scarring, nerve palsy, and encephalitis in the case with disseminated zoster. […] Antiviral therapy hastens the resolution of lesions, decreases acute pain and helps to prevent post-herpetic neuralgia especially in elderly patients. Acyclovir 800 mg, five times daily for five days, valacyclovir 1 gm three times daily for five days, and famciclovir 500 mg three times daily for seven days are the antiviral drugs used to treat herpes zoster.
#78 Clinical Overview of Shingles (Herpes Zoster) | Shingles (Herpes Zoster) | CDC
https://www.cdc.gov/shingles/hcp/clinical-overview/index.html
Treatment is most effective within 72 hours of symptom onset. Diagnose and treat early to prevent progressive corneal involvement and potential vision loss. […] These antivirals accelerate the resolution of lesions; reduce the development of new lesions and viral shedding; and decrease the severity of acute pain.
#79 Clinical Overview of Shingles (Herpes Zoster) | Shingles (Herpes Zoster) | CDC
https://www.cdc.gov/shingles/hcp/clinical-overview/index.html
Treatment is most effective within 72 hours of symptom onset. Diagnose and treat early to prevent progressive corneal involvement and potential vision loss. […] These antivirals accelerate the resolution of lesions; reduce the development of new lesions and viral shedding; and decrease the severity of acute pain.