Zespół oddechowy bliskiego wschodu (mers)
Patofizjologia i mechanizm

Zespół oddechowy Bliskiego Wschodu (MERS) wywoływany przez koronawirusa MERS-CoV charakteryzuje się wysoką śmiertelnością około 35%. Wirus ten, będący betakoronawirusem o genomie RNA dodatniej polarności (~30 tys. nukleotydów), wykorzystuje białko kolca (S) do wiązania z receptorem DPP4 (CD26) na powierzchni komórek gospodarza, co determinuje tropizm tkankowy, głównie do nieorzęsionych komórek nabłonka dolnych dróg oddechowych. MERS-CoV wykazuje unikalną zdolność do infekcji makrofagów, komórek dendrytycznych oraz limfocytów T, co prowadzi do modulacji odpowiedzi immunologicznej, indukcji apoptozy limfocytów T i opóźnionej odpowiedzi prozapalnej. Geny wirusa, takie jak ORF4a, ORF4b, ORF5 i ORF8b, pełnią funkcje antagonistów interferonu typu I, co osłabia odpowiedź przeciwwirusową i sprzyja ciężkiemu przebiegowi choroby, zwłaszcza u pacjentów z chorobami współistniejącymi (przewlekła choroba płuc, cukrzyca, niewydolność nerek). W modelach zwierzęcych, miano wirusa w płucach osiąga szczyt 2 dni po zakażeniu, a liczba neutrofili we krwi obwodowej koreluje z ciężkością choroby, co może mieć zastosowanie prognostyczne u ludzi.

  1. Patogeneza zespołu oddechowego Bliskiego Wschodu (MERS)
    1. Pochodzenie i rezerwuar wirusa
    2. Charakterystyka molekularna wirusa
  2. Mechanizm infekcji i wnikania do komórek
    1. Rola receptora DPP4
    2. Proces wnikania wirusa do komórki
  3. Mechanizmy patogenezy MERS-CoV
    1. Replikacja wirusa i uszkodzenie komórek
    2. Interakcje wirusa z układem odpornościowym
    3. Mechanizmy unikania odpowiedzi immunologicznej
  4. Czynniki gospodarza wpływające na patogenezę
    1. Wpływ stanów współistniejących
    2. Badania na modelach zwierzęcych
    3. Różnice międzygatunkowe w patogenezie
  5. Powikłania kliniczne związane z patogenezą MERS
    1. Objawy układu oddechowego
    2. Powikłania pozapłucne
    3. Grupa ryzyka i czynniki prognostyczne
  6. Implikacje dla strategii terapeutycznych
    1. Potencjalne cele terapeutyczne
    2. Strategie zapobiegania i kontroli
    3. Kolejne rozdziały

Patogeneza zespołu oddechowego Bliskiego Wschodu (MERS)

Zespół oddechowy Bliskiego Wschodu (MERS) jest wysoce zakaźną chorobą wywoływaną przez koronawirusa MERS-CoV, który został po raz pierwszy zidentyfikowany w Arabii Saudyjskiej w 2012 roku. Ten betakoronawirus charakteryzuje się wysoką śmiertelnością, wynoszącą około 35%, co czyni go jednym z najbardziej niebezpiecznych koronawirusów dla człowieka.12 Zrozumienie patogenezy MERS-CoV jest kluczowe dla opracowania skutecznych strategii terapeutycznych i zapobiegawczych.

Pochodzenie i rezerwuar wirusa

MERS-CoV jest wirusem odzwierzęcym, którego pochodzenie prawdopodobnie związane jest z nietoperzami. Badania wykazały, że wirus jest blisko spokrewniony z koronawirusami nietoperzy Tylonycteris bat coronavirus HKU4 i Pipistrellus bat coronavirus HKU5.1 Jednakże obecnym głównym rezerwuarem wirusa są wielbłądy jednogarbne (dromadery), które stanowią kluczowe ogniwo w transmisji wirusa do ludzi.23

Wyniki badań filogenetycznych sugerują, że MERS-CoV pojawił się u wielbłądów w wyniku zdarzeń rekombinacyjnych w obrębie białka kolca (spike) wielbłądów afrykańskich, po czym rozprzestrzenił się na Półwysep Arabski.1 Badania seroepidemiologiczne wykazały, że wirus krąży wśród populacji wielbłądów od dziesięcioleci, co wskazuje na efektywną transmisję MERS-CoV w tym gatunku.2

Charakterystyka molekularna wirusa

MERS-CoV jest osłonkowym wirusem RNA o dodatniej polarności, którego genom liczy ponad 30 tysięcy nukleotydów. Genom zawiera siedem przewidywanych otwartych ramek odczytu (ORF1a, ORF1b, ORF3, ORF4a, ORF4b, ORF5 i ORF8b) oraz cztery geny strukturalne (S, E, M, N).1 Dwie ramki odczytu (ORF1a, ORF1b) kodują kompleks replikazy, natomiast pozostałe pięć ORF koduje pięć białek dodatkowych, które odgrywają kluczową rolę w infekcji i patogenezie.

Białko kolca (S) MERS-CoV jest białkiem transmembranowym składającym się z dwóch podjednostek: S1 i S2. Podjednostka S1 zawiera domenę wiążącą receptor (RBD), która przyłącza się do receptora dipeptydylopeptydazy 4 (DPP4, znany również jako CD26) gospodarza.23 Białko kolca MERS-CoV odgrywa kluczową rolę w patogenezie wirusa, umożliwiając jego wniknięcie do komórek gospodarza.

Mechanizm infekcji i wnikania do komórek

Rola receptora DPP4

Kluczowym elementem w patogenezie MERS-CoV jest interakcja białka kolca wirusa z receptorem DPP4 gospodarza. DPP4 jest wielofunkcyjnym białkiem błonowym typu II z długą domeną zewnątrzkomórkową i krótkim, sześcioaminokwasowym ogonem cytoplazmatycznym.1 Podczas infekcji, MERS-CoV wiąże się z domeną zewnątrzkomórkową DPP4, aby uzyskać dostęp do komórki gospodarza.

Istotne jest rozmieszczenie receptorów DPP4 w organizmie, gdyż determinuje ono tropizm tkankowy wirusa. Receptory DPP4 znajdują się na powierzchni nabłonkowej różnych ludzkich narządów, takich jak płuca, nerki, wątroba, szpik kostny, grasica i jelita.23 Ta szeroka dystrybucja receptora może wyjaśniać różnorodność objawów klinicznych obserwowanych u pacjentów z MERS.

Co istotne, ekspresja DPP4 różni się między gatunkami, co wpływa na podatność na zakażenie MERS-CoV. Na przykład, jama nosowa i jelito cienkie wielbłądów wykazują wysoką ekspresję DPP4, co może zwiększać potencjał transmisji międzygatunkowej MERS-CoV.4 Natomiast myszy są odporne na zakażenie MERS-CoV, ponieważ mysi DPP4 (mDPP4) nie wspiera wnikania MERS-CoV z powodu dwóch różnic aminokwasowych w regionie wchodzącym w interakcję z białkiem kolca.5

Proces wnikania wirusa do komórki

Cykl infekcyjny koronawirusów rozpoczyna się od wiązania glikoproteiny kolca wirusa z receptorem na powierzchni komórki gospodarza, co uruchamia sygnalizację receptorową i umożliwia internalizację wirusa.1 W przypadku MERS-CoV, proces wnikania może odbywać się zarówno poprzez bezpośrednią fuzję błon, jak i endocytozę.

Wiązanie białka S MERS-CoV do receptorów komórkowych gospodarza prowadzi do przyczepiania się i rozpoczęcia infekcji. Następnie dochodzi do fuzji osłonki wirusowej z błoną komórkową gospodarza, wywołanej rozcięciem białek S, ułatwionego przez proteazy komórkowe.2

Badania wykazały, że białko S MERS-CoV jest rozcinane w dwóch krokach przez proteazę furynową – jeden podczas syntezy białka kolca, a drugi później, podczas wnikania do komórki gospodarza.3 Te miejsca cięcia przez furynę są obserwowane w białku S MERS-CoV wyizolowanym od wielbłądów, a nabywanie miejsc cięcia poprzez mutacje mogło umożliwić wirusowi zakażanie większej liczby typów komórek u wielbłądów i łatwiejsze rozprzestrzenianie się poprzez wydzieliny i płyny tych zwierząt.

Co ciekawe, badania wykazały, że ogon cytoplazmatyczny DPP4 nie jest kluczowy dla internalizacji MERS-CoV. Wskazuje to, że po związaniu się MERS-CoV z DPP4, inne białko gospodarza może wyzwalać proces internalizacji.4 MERS-CoV może wchodzić w interakcje z innymi czynnikami gospodarza, takimi jak kwas sialowy, tetraspanina, proteazy gospodarza TMPRSS2 lub inne nieznane czynniki, które przyczyniają się do internalizacji wirusa.

Mechanizmy patogenezy MERS-CoV

Replikacja wirusa i uszkodzenie komórek

MERS-CoV wykazuje silny tropizm do nieorzęsionych komórek nabłonkowych oskrzeli, co jest unikalne, ponieważ większość wirusów oddechowych atakuje komórki rzęskowe.1 Po wniknięciu do komórki gospodarza, MERS-CoV wykorzystuje maszynerię komórkową do replikacji swojego materiału genetycznego i produkcji nowych cząstek wirusa.

Nsp1 (niestrukturalne białko 1) MERS-CoV jest istotnym czynnikiem zjadliwości, który ułatwia biologiczne działania wirusa. Nsp1 hamuje ekspresję genów gospodarza w zakażonych komórkach i promuje montaż lub pączkowanie wirusa in vitro, co prowadzi do wydajnej replikacji wirusa.2

Zakażenie komórek nabłonkowych MERS-CoV prowadzi do indukcji wolnej, ale znaczącej odpowiedzi interferonów typu I i II.3 Jednakże MERS-CoV, w przeciwieństwie do innych wirusów, wywołuje opóźnioną odpowiedź prozapalną i osłabia odporność wrodzoną, co sugeruje, że MERS-CoV jest bardziej śmiertelny w porównaniu z SARS-CoV.45

Interakcje wirusa z układem odpornościowym

MERS-CoV wykazuje zdolność do modulowania odpowiedzi immunologicznej gospodarza, co przyczynia się do jego wysokiej patogenności. Infekcja MERS-CoV komórek nabłonka indukuje uwalnianie prozapalnych chemokin i cytokin z makrofagów pochodzących z monocytów. Uważa się, że te chemokiny/cytokiny powodują zmiany zapalne i uszkodzenia tkanek poprzez infiltrację komórek odpornościowych w dolnych drogach oddechowych.5

MERS-CoV może skutecznie infekować ludzkie komórki dendrytyczne i makrofagi, co pomaga wirusowi w dysregulacji układu odpornościowego.1 Te fagocyty działają jak rezerwuary i środki transportu dla tych wirusów, pomagając w replikacji i rozprzestrzenianiu się, podobnie jak wirus HIV.6

Co więcej, MERS-CoV ma zdolność do infekowania ludzkich limfocytów T poprzez wysoką ekspresję CD26, prowadząc do apoptozy limfocytów T, co potencjalnie zakłóca przeciwwirusową odpowiedź limfocytów T.23

Z obecnej wiedzy wynika, że replikacja wirusa w makrofagach powoduje ekstremalną cytotoksyczność i wyzwala indukcję prozapalnych czynników chemicznych, które mogą prowadzić do powikłań związanych z MERS.7

Mechanizmy unikania odpowiedzi immunologicznej

MERS-CoV rozwinął liczne mechanizmy antagonistyczne, aby osłabić indukcję przeciwwirusowych i prozapalnych cytokin w zainfekowanych komórkach nabłonkowych.1 Białko M oraz białka dodatkowe MERS-CoV, w tym ORF4a, ORF4b i ORF5, zostały udowodnione jako antagoniści sygnalizacji interferonu typu I (IFN-I) i hamują produkcję genów stymulowanych interferonem (ISG).3

Białko ORF8b kodowane przez MERS-CoV jest silnym antagonistą szlaku sygnałowego receptorów podobnych do RIG-I (RLR). ORF8b znacząco obniża indukcję aktywności promotora IFN-β zależną od MDA5 i RIG-I. Co ciekawe, ORF8b wydaje się regulować MDA5 i RIG-I w odmienny sposób, gdyż poziomy białka MDA5 były znacznie obniżone, podczas gdy poziomy RIG-I pozostawały w dużej mierze niezmienione.23

ORF8b wydaje się hamować wszystkie formy RIG-I (pełnej długości, RIG-I-1-734 i RIG-I-1-228), co sugeruje, że może hamować interakcje CARD-CARD między RIG-I a MAVS bez wpływu na poziomy białka RIG-I, prowadząc do niższych poziomów fosforylacji IRF3.4

Zmniejszona ekspresja IFN, genów indukowanych kwasem retinowym (RIG)-1, melanoma differentiation associate (MDA5) i czynników regulatorowych interferonu IRF-3 i IRF-7 została zaobserwowana w popłuczynach oskrzelowo-pęcherzykowych (BAL) i surowicy pacjentów w zaawansowanych stadiach MERS.6

Czynniki gospodarza wpływające na patogenezę

Wpływ stanów współistniejących

Nasilenie infekcji MERS-CoV jest stosunkowo większe u pacjentów ze współistniejącymi schorzeniami, takimi jak przewlekła choroba płuc, niewydolność nerek, cukrzyca i inne stany z upośledzoną odpornością.8 Badania sugerują, że wcześniej istniejące schorzenia płuc mogą zwiększać szanse na zachorowanie na MERS, ponieważ przewlekłe choroby płuc prowadzą do zwiększonej ekspresji DPP4.9

Podwyższona ekspresja DPP4 w pneumocytach typu I i niewystarczająca odpowiedź interferonu typu I mogą być kluczowymi czynnikami determinującymi ciężkie zakażenie MERS-CoV.10 Ponadto, DPP4 jest raportowana jako czynnik chemorepelentny dla neutrofili; dlatego zmiany w uwalnianiu DPP4 podczas infekcji MERS-CoV mogą wpływać na skład infiltratu immunologicznego, a ostatecznie na wynik zakażenia.11

Badania na modelach zwierzęcych

Brak danych z autopsji pacjentów oraz dobrych modeli zwierzęcych utrudnia zrozumienie odporności i patogenezy zakażenia MERS-CoV.1 Jednakże, badania na modelach zwierzęcych dostarczyły pewnych informacji na temat patogenezy MERS.

W modelu mysim MERS-CoV, miano wirusa w płucach osiąga szczyt 2 dni po zakażeniu, jednocześnie z limfopenią i neutrofilią we krwi obwodowej, dwoma zjawiskami obserwowanymi również w zakażeniu MERS-CoV u ludzi.2 Co ważne, liczba neutrofili w 1 dniu po zakażeniu była predykcyjna dla ciężkości choroby przy śmiertelnej dawce MERS-CoV, podkreślając wartość predykcyjną hematologii w tym modelu.3

Jedyny dostępny raport z autopsji, pochodzący z przypadku z kwietnia 2014 roku w Zjednoczonych Emiratach Arabskich, identyfikuje pneumocyty pęcherzykowe typu 2 i wielojądrzaste komórki syncytialne układu oddechowego o niepewnym pochodzeniu jako główne cele MERS-CoV. Zgodnie z tropizmem do komórek dolnych dróg oddechowych, główną obserwowaną patologią było rozlane uszkodzenie pęcherzyków płucnych, a także zaobserwowano dowody na patologię immunologiczną w niezakażonych obszarach płuc.4

Różnice międzygatunkowe w patogenezie

Patogeneza MERS-CoV różni się znacznie między gatunkami. U wielbłądów, MERS-CoV powoduje przejściową, łagodną chorobę; jednak duże ilości MERS-CoV są wydzielane z górnych dróg oddechowych, zgodnie z przeważającą replikacją MERS-CoV w małżowinach nosowych i krtani u tych zwierząt, co wyjaśnia częstą transmisję odzwierzęcą.1

Chociaż objawy kliniczne, a także transmisja, znacznie różnią się u ludzi i wielbłądów zakażonych MERS-CoV, wirusy wyizolowane z tych dwóch gatunków są bardzo podobne, jeśli nie identyczne. Wskazuje to, że czynniki gospodarza odgrywają znaczącą rolę w patogenezie i transmisji MERS-CoV.2

Wirus MERS-CoV atakuje bezpośrednio dolne drogi oddechowe (pneumocyty) u wielbłądów dromedary i nadal replikuje się preferencyjnie w komórkach dróg oddechowych górnych dróg oddechowych. Efekty cytopatyczne wirusa wyraźnie pokazują wyraziste tworzenie się syncytium u ludzi, a także u naczelnych niebędących ludźmi.3

Cecha Ludzie Wielbłądy
Główne miejsce replikacji wirusa Dolne drogi oddechowe (pneumocyty) Górne drogi oddechowe (małżowiny nosowe, krtań)
Nasilenie objawów Od bezobjawowego do ciężkiego zapalenia płuc Łagodna, przejściowa choroba
Wydzielanie wirusa Wyższy ładunek wirusowy w dolnych drogach oddechowych Duże ilości wirusa wydzielane z górnych dróg oddechowych
Ekspresja receptora DPP4 Wyższa w dolnych drogach oddechowych Wysoka w jamie nosowej i jelicie cienkim
Potencjał transmisji Ograniczona transmisja między ludźmi Efektywna transmisja w populacji wielbłądów

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Powikłania kliniczne związane z patogenezą MERS

Objawy układu oddechowego

MERS-CoV powoduje ostrą, wysoce śmiertelną postać zapalenia płuc i zaburzenia czynności nerek.1 Patogeneza wirusa prowadzi do szerokiego spektrum objawów klinicznych, od zakażenia bezobjawowego do ciężkiego zapalenia płuc. W ciężkich przypadkach może rozwinąć się niewydolność oddechowa, która wymaga wentylacji mechanicznej lub wsparcia na oddziale intensywnej terapii.2

Główną obserwowaną patologią jest rozlane uszkodzenie pęcherzyków płucnych, co jest zgodne z tropizmem wirusa do komórek dolnych dróg oddechowych.3 MERS-CoV wykazuje silny tropizm do nieorzęsionych komórek nabłonkowych oskrzeli, co jest unikalne, ponieważ większość wirusów oddechowych atakuje komórki rzęskowe.4

W porównaniu z innym członkiem tej rodziny wirusów, znanym jako koronawirus zespołu ostrej niewydolności oddechowej (SARS-CoV), MERS-CoV ma skłonność do ustanawiania produktywnej infekcji w makrofagach i komórkach dendrytycznych. Może to z kolei wywoływać uwalnianie prozapalnych cytokin, skutkując przedłużonym stanem zapalnym i uszkodzeniem tkanek, co klinicznie objawia się jako ciężka postać zapalenia płuc i niewydolności oddechowej.5

Powikłania pozapłucne

Główne powikłania zgłaszane w przypadkach śmiertelnych to hiperkaliemia związana z tachykardią komorową, rozsiane wykrzepianie wewnątrznaczyniowe, zapalenie osierdzia i niewydolność wielonarządowa.3 MERS-CoV może powodować dodatkowe powikłania, takie jak niewydolność nerek.4

Chociaż dane z badań klinicznych, in vitro i ex vivo sugerowały potencjał do rozprzestrzeniania się wirusa, zajęcie narządów pozapłucnych u pacjentów z MERS nie zostało potwierdzone z powodu braku badania autopsyjnego.6 MERS-CoV może być wykrywany z wyższym ładunkiem wirusowym i przez dłuższy czas w dolnych drogach oddechowych niż w górnych drogach oddechowych, a także został wykryty w kale, surowicy, moczu i próbkach krwi.7

Grupa ryzyka i czynniki prognostyczne

Współczynnik śmiertelności w przypadku MERS-CoV (około 35%) jest wyższy niż w przypadku SARS-CoV (9,6%).4 Ciężkość choroby jest większa u osób z istniejącymi wcześniej schorzeniami, takimi jak przewlekła choroba płuc, niewydolność nerek, cukrzyca i inne stany z upośledzoną odpornością.9

Neutrofilia we krwi obwodowej może służyć jako biomarker predykcyjny ciężkiej choroby MERS-CoV u myszy, podobnie jak podwyższony poziom neutrofili w momencie przyjęcia pacjentów z SARS przewidywał niekorzystne wyniki u ludzi.8 To podkreśla wartość badań hematologicznych w prognozowaniu przebiegu choroby.

Liczba neutrofili w pierwszym dniu po zakażeniu była predykcyjna dla ciężkości choroby przy śmiertelnej dawce MERS-CoV, co podkreśla wartość predykcyjną hematologii w modelu mysim.9 Te wyniki mogą mieć zastosowanie kliniczne w przewidywaniu przebiegu choroby u ludzi.

Implikacje dla strategii terapeutycznych

Potencjalne cele terapeutyczne

Zrozumienie patogenezy MERS-CoV otwiera drzwi do opracowania skutecznych strategii terapeutycznych. Replikacja MERS-CoV jest wysoce wrażliwa na leczenie interferonem typu I (IFN-I) w hodowli komórkowej, co sugeruje, że leczenie IFN-I może być możliwym podejściem terapeutycznym w praktyce klinicznej.4

Białko kolca MERS-CoV, które odpowiada za wniknięcie MERS-CoV, jest uważane za kluczowy cel rozwoju szczepionki przeciwko zakażeniu MERS-CoV.12 Neutralizujące przeciwciała monoklonalne wiążą się z białkiem kolca MERS-CoV i zapobiegają wnikaniu wirusa i następnej fuzji błon, tym samym hamując replikację wirusa i zmniejszając objawy kliniczne u modeli zwierzęcych i ludzi.

Badacze z Texas Children’s CVD i ich współpracownicy oparli rozwój szczepionki na segmencie białka kolca SARS-CoV lub MERS-CoV, znanym jako domena wiążąca receptor (RBD). Idea polega na tym, że szczepionki stymulowałyby przeciwciała neutralizujące, które blokowałyby przyłączanie się wirusa do jego receptora na komórce gospodarza, zapobiegając w ten sposób zakażeniu koronawirusami. Badacze wykazali, że kandydat na szczepionkę RBD wywołuje silną odpowiedź przeciwciał neutralizujących i chroni zaszczepione zwierzęta przed infekcją wirusem wyzwania.3

Strategie zapobiegania i kontroli

Z powodu braku specyficznego leczenia i szczepionki, kluczowe znaczenie mają środki zapobiegania i kontroli zakażeń. Transmisja MERS-CoV odbywa się poprzez bliski kontakt z zakażonymi osobami lub zwierzętami, głównie poprzez zakażenie kropelkowe.3

WHO zaleca, aby wszystkie osoby mające kontakt z osobami podejrzanymi o MERS (oprócz standardowych środków ostrożności): nosiły maskę medyczną, nosiły ochronę oczu (tj. gogle lub przyłbicę), nosiły czystą, niesterylną, długą zapinaną na rękawy odzież; oraz rękawiczki (niektóre procedury mogą wymagać sterylnych rękawiczek).4

MERS-CoV przetrwał lepiej niż wirusy A(H1N1) na powierzchniach nieożywionych i ma zdolność do pozostawania żywym w aerozolu.8 Dlatego środki zapobiegania i kontroli zakażeń mają kluczowe znaczenie dla zapobiegania możliwemu rozprzestrzenianiu się MERS-CoV w placówkach opieki zdrowotnej.5

WHO nadal współpracuje ze specjalistami ds. zdrowia publicznego i zdrowia zwierząt, klinicystami i naukowcami w dotkniętych i zagrożonych państwach członkowskich w celu gromadzenia i udostępniania dowodów naukowych, aby lepiej zrozumieć wirusa i chorobę, którą powoduje.6

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  1. 17.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. […] A large amount of information is now available regarding the virus, its structure, route of transmission and its pathophysiology. Therefore, this review summarizes the current understanding of MERS-CoV’s pathogenesis, treatment options and recent scientific advancements in vaccine and other therapeutic developments, and the major steps taken for MERS prevention control. […] Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a zoonotic virus, whose mode of transmission is from animals to humans. The origin of the virus is believed to be bats, from which it was then transferred to camels. Camels are currently regarded as a major host for MERS-CoV. […] The pathogenic agent of Middle East respiratory syndrome is a new coronavirus which was initially identified from the respiratory content of a patient who was infected, and died, as a result of infection from a mysterious viral disease showing pneumonia like symptoms in Saudi Arabia in 2012. […] The understanding of MERS-CoV pathogenesis has been limited due to nonavailability of patient autopsy or pathological samples from the patients. Our understanding of the disease pathogenesis is based entirely on in vitro studies. […] The severity of MERS-CoV infection is relatively more in patients with co-morbid conditions, such as chronic lung disease, renal failure, diabetes and others with compromised immune systems.
  • #1 MERS-related coronavirus – Wikipedia
    https://en.wikipedia.org/wiki/MERS-related_coronavirus
    Further research identified dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional cellular receptor for MERS-CoV. Unlike other known coronavirus receptors, the enzymatic activity of DPP4 is not required for infection. […] The virus appears to have originated in bats. The virus itself has been isolated from a bat. This virus is closely related to the Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5. […] Research has linked camels, showing that the coronavirus infection in dromedary camel calves and adults is a 99.9% match to the genomes of human clade B MERS-CoV.
  • #1
    https://jws.rivierapublishing.id/index.php/jws/article/view/1226
    Middle East Respiratory Syndrome (MERS) is a zoonotic disease caused by MERS-CoV, a beta coronavirus with a mortality rate of approximately 35%. […] This study explores MERS-CoV’s epidemiology, pathogenesis, and transmission dynamics, aiming to enhance understanding of its replication, spread, and control strategies due to limited pharmaceutical interventions. […] Findings indicate that MERS-CoV originated from recombination events in the spike protein of African dromedaries and spread to the Arabian Peninsula via camels. […] The findings emphasize the high pandemic potential of MERS-CoV due to its mortality rate and lack of effective treatments, highlighting the need for strict infection control and further research into viable therapeutic options. […] Zhou, J., Chu, H., Chan, J. F.-W., Yuen, K.-Y. (2015). Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis. Virology Journal, 12, 17.
  • #1 MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges | Annals of Clinical Microbiology and Antimicrobials | Full Text
    https://ann-clinmicrob.biomedcentral.com/articles/10.1186/s12941-020-00414-7
    The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. […] The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. […] The genomic profile of MERS-CoV is over thirty thousand nucleotides in length, with seven predicted open reading frames (ORFs) (ORF1a, ORF1b, ORF3, ORF4a, ORF4b, ORF5 and ORF8b) and four structural genes (S, E, M, N). […] The two ORFs (ORF1a, ORF1b) encodes replicase complex whereas remaining five accessory ORFs encodes five accessory proteins which play a crucial role in the infection and pathogenesis.
  • #1 Middle East respiratory syndrome coronavirus (MERS-CoV) internalization does not rely on DPP4 cytoplasmic tail signaling | npj Viruses
    https://www.nature.com/articles/s44298-024-00080-y
    Middle East respiratory syndrome coronavirus (MERS-CoV) infects respiratory epithelial cells in humans and camels by binding to dipeptidyl peptidase 4 (DPP4) as its entry receptor. DPP4 is a multifunctional type II membrane protein with a long ectodomain and a short six-amino-acid (aa) cytoplasmic tail. MERS-CoV is known to bind to the ectodomain of DPP4 to gain entry into the host cell. However, the role of the cytoplasmic tail in the entry process remains unclear. […] Overall, these data suggest that, although MERS-CoV binds to DPP4, other host factors may need to interact with DPP4 or the spike protein to trigger internalization. […] MERS-CoV uses dipeptidyl peptidase 4 (DPP4) as an entry receptor, which belongs to the serine peptidase family and is predominantly expressed in epithelial cells of the lungs, liver, kidney, intestine, thymocytes, and alveolar macrophages. The distribution of DPP4 in host cells plays a vital role in the transmission of MERS-CoV between camels and humans, as well as the severity of the infection. […] In contrast, the nasal cavity and small intestine of camels showed a high expression of DPP4, which has the potential to enhance the cross-species transmission of MERS-CoV.
  • #1 Middle East respiratory syndrome coronavirus (MERS-CoV) internalization does not rely on DPP4 cytoplasmic tail signaling | npj Viruses
    https://www.nature.com/articles/s44298-024-00080-y
    The infection cycle of coronaviruses begins with the binding of virus spike glycoprotein to the receptor on the host cell surface, which triggers receptor signaling and allows the virus to internalize and enter the cells. […] However, despite molecular and structural insights into MERS-CoV and the role and involvement of other host factors in entry, understanding of how DPP4 signaling pathways actively drive virus/receptor complex internalization is limited. MERS-CoV internalization might be triggered by DPP4 alone or along with other host factors such as sialic acid, tetraspanin, host proteases TMPRSS2, or other unknown host factor(s) to contribute to virus internalization. […] In this study, we showed that the DPP4 cytoplasmic tail is not crucial for MERS-CoV internalization. Our initial findings demonstrate that MERS-CoV can enter cells via direct membrane fusion and endocytosis. […] These findings demonstrate that the absence of the cytoplasmic tail, DPP4 presented on the cell membrane, allows for the binding of the MERS-CoV spike protein and its subsequent internalization into host cells. Therefore, we speculate that MERS-CoV binds to DPP4, and following receptor binding, another host protein may trigger its internalization process.
  • #1 MERS-related coronavirus – Wikipedia
    https://en.wikipedia.org/wiki/MERS-related_coronavirus
    Middle East respiratory syndromerelated coronavirus (MERS-CoV) is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the DPP4 receptor. […] MERS-CoV is one of seven known coronaviruses to infect humans, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, the original SARS-CoV (or SARS-CoV-1), and SARS-CoV-2. It has frequently been referred to as a SARS-like virus. […] In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells, and it has been shown to effectively evade the innate immune responses and antagonize interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells.
  • #1 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/17343
    Several factors could be involved in MERS pathogenesis, including viral and host factors, interferon induction, dysregulation of cytokines and adaptive immune responses. […] MERS-CoV could efficiently infect human dendritic cells and macrophages in vitro which would help the virus to dysregulate the immune system. […] MERS-CoV also has the ability to infect T cells through their highly expression of CD26, leading to T cell apoptosis, which might potentially disrupt anti-viral T cell responses. […] MERS-CoV replication is highly sensitive to type I interferon (IFN-I) treatment in cell culture suggesting that IFN-I treatment could be a possible therapeutic approach in clinical practice. […] MERS-CoV structural and accessory proteins, including M, ORF4a, ORF4b, and ORF5 had all been proved that could antagonize IFN-I signaling and inhibit ISG productions.
  • #1 Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis | Virology Journal | Full Text
    https://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0446-6
    Although data from clinical, in vitro and ex vivo studies suggested the potential for virus dissemination, extrapulmonary involvement in MERS patients has not been ascertained due to the lack of autopsy study. […] More research findings on the pathogenesis of MERS and the tissue tropisms of MERS-CoV may help to improve the treatment and infection control of MERS. […] The pathogenesis of human MERS-CoV infection remains poorly understood. […] However, MERS-CoV has evolved multiple antagonistic mechanisms to attenuate the induction of antiviral and proinflammatory cytokines in the affected epithelial cells. […] Additionally, MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, which elicits the aberrant production of proinflammatory cytokines/chemokines. […] MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells. […] More studies are warranted to further characterize the tissue tropisms of MERS-CoV for the better understanding towards the pathogenesis of MERS.
  • #1 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/17343
    Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel betacoronavirus (MERS coronavirus, MERS-CoV). […] However, the epidemiology of MERS as well as immune responses against the virus in animal models and patients are still not well understood, hindering the vaccine and therapeutic developments. […] MERS-CoV continuously crosses species and transmits from dromedary camels and/or bats to human population, which poses a significant threat to public health. […] Previous studies indicated that MERS-CoV infection are primarily due to repeated introductions of MERS-CoV from dromedary camels to human, while human to human transmission is limited. […] The lack of human autopsy data as well as good animal models hindered our understanding on the immunity and pathogenesis of MERS-CoV infection.
  • #1 SARS and MERS: recent insights into emerging coronaviruses | Nature Reviews Microbiology
    https://www.nature.com/articles/nrmicro.2016.81
    SARS-CoV and MERS-CoV use several strategies to avoid the innate immune response. […] The pathogenesis of MERS-CoV in dromedary camels has been studied experimentally in a limited number of animals. These animals developed transient mild disease; however, large quantities of MERS-CoV were shed from the upper respiratory tract, in line with the predominant replication of MERS-CoV in the nasal turbinates and larynx in these animals, which explains the frequent zoonotic transmission.
  • #1 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. […] A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. […] Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. […] MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. […] The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. […] The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). […] The DPP4 has been reported as a neutrophil chemo repellent; therefore, the variations in DPP4 shedding during MERS-CoV infection could influence the composition of the immune infiltrate, and ultimately to the outcome of the infection.
  • #1 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/17343
    The spike protein of MERS-CoV, which is responsible for MERS-CoV entry is considered as a key target for vaccine development against MERS-CoV infection. […] The protective role of virus specific CD4T cells is less studied, especially in respiratory CoV infections. […] Understanding these basic informations will not only enhance emerging CoV research but also will aid our public health preparedness against MERS-CoV.
  • #2 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. […] A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. […] Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. […] MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. […] The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. […] The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). […] The DPP4 has been reported as a neutrophil chemo repellent; therefore, the variations in DPP4 shedding during MERS-CoV infection could influence the composition of the immune infiltrate, and ultimately to the outcome of the infection.
  • #2 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. […] A large amount of information is now available regarding the virus, its structure, route of transmission and its pathophysiology. Therefore, this review summarizes the current understanding of MERS-CoV’s pathogenesis, treatment options and recent scientific advancements in vaccine and other therapeutic developments, and the major steps taken for MERS prevention control. […] Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a zoonotic virus, whose mode of transmission is from animals to humans. The origin of the virus is believed to be bats, from which it was then transferred to camels. Camels are currently regarded as a major host for MERS-CoV. […] The pathogenic agent of Middle East respiratory syndrome is a new coronavirus which was initially identified from the respiratory content of a patient who was infected, and died, as a result of infection from a mysterious viral disease showing pneumonia like symptoms in Saudi Arabia in 2012. […] The understanding of MERS-CoV pathogenesis has been limited due to nonavailability of patient autopsy or pathological samples from the patients. Our understanding of the disease pathogenesis is based entirely on in vitro studies. […] The severity of MERS-CoV infection is relatively more in patients with co-morbid conditions, such as chronic lung disease, renal failure, diabetes and others with compromised immune systems.
  • #2 Host Determinants of MERS-CoV Transmission and Pathogenesis
    https://www.mdpi.com/1999-4915/11/3/280
    This review highlights the role of some MERS-CoV-interacting host factors—especially DPP4—in MERS-CoV pathogenesis and transmission. […] MERS-CoV infection in these animals merely causes mild upper respiratory tract infection, but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species. […] Although the clinical manifestations, as well as transmission, are remarkably different in MERS-CoV-infected humans and dromedary camels, the viruses isolated from these two species are highly similar, if not indistinguishable. […] This indicates that host factors play a significant role in MERS-CoV pathogenesis and transmission. […] DPP4 is the functional receptor of MERS-CoV; its absence renders cells resistant to this virus, while its transient expression in non-susceptible cells permits viral replication.
  • #2 MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges | Annals of Clinical Microbiology and Antimicrobials | Full Text
    https://ann-clinmicrob.biomedcentral.com/articles/10.1186/s12941-020-00414-7
    The S protein of MERS-CoV is a transmembrane protein having two subunits S1 and S2. The S1 subunit has a receptor-binding domain (RBD) that binds with dipeptidyl peptidase 4 (DPP4) receptor of the host. […] MERS-CoV utilises cellular DPP4 receptor of the host for cell entry through binding of its S protein. […] Binding of S protein of MERS-CoV to the host cellular receptors results in attachment and start of an infection. This is to follow by fusion of viral envelope with host cell membrane triggered by cleavage of S proteins facilitated by cellular proteases. […] Specific mutations in a receptor-binding domain on N terminal of the S protein have been shown to determine its cross-species infection capabilities. […] Studies have also established the role of heptad repeat regions in C-terminal of MERS-CoV and related coronaviruses in cross-species transmission.
  • #2 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    Before the discovery of MERS-CoV, SARS-CoV was considered the most pathogenic coronavirus. However, the higher pathogenicity of MERS-CoV was apparent by the higher number of deaths caused by this virus. […] MERS-CoV can also induce pro-inflammatory cytokines but lacks in production of innate antiviral cytokines compared with SARS-CoV. Suggesting MERS-CoV induces delayed pro-inflammatory response and attenuates innate immunity, which suggests that MERS-CoV is more lethal compared with SARS-CoV. […] Primarily the MERS virus interacts with the host DPP4 receptor through its spike (S) protein after entering the respiratory tract. DPP4 receptors are present on the epithelial surface of various human organs such as, the lungs, kidneys, liver, bone marrow, thymus and intestines. […] Recent findings have suggested that a prior existing pulmonary ailment might increase the chances of such individuals contracting MERS, as chronic pulmonary diseases results in enhanced DPP4 expression.
  • #2 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    CoV nsp1 is a serious virulence factor, which facilitates the biological actions of MERS-CoV. Studying the nsp1 can advance our understanding of pathogenicity of MERS-CoV and facilitate development of better therapeutics. Host gene expression in infected cells is suppressed by MERS-CoV nsp1, which also promotes virus assembly or budding in in vitro, leading to efficient virus replication, suggesting nsp1 is also critical for MERS-CoV replication and promotes production of virus particles in the host. […] The infection with MERS-CoV of human epithelial cells induces the release of pro-inflammatory chemokines and cytokines from the monocyte-derived macrophages. It is believed that these chemokines/cytokines cause inflammatory changes and tissue injury through infiltration of immune cells in the lower respiratory tract. […] Thus, these phagocytes act like reservoirs and means of transportation for these viruses, helping to replicate and disseminate, such as the HIV virus.
  • #2 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/17343
    Several factors could be involved in MERS pathogenesis, including viral and host factors, interferon induction, dysregulation of cytokines and adaptive immune responses. […] MERS-CoV could efficiently infect human dendritic cells and macrophages in vitro which would help the virus to dysregulate the immune system. […] MERS-CoV also has the ability to infect T cells through their highly expression of CD26, leading to T cell apoptosis, which might potentially disrupt anti-viral T cell responses. […] MERS-CoV replication is highly sensitive to type I interferon (IFN-I) treatment in cell culture suggesting that IFN-I treatment could be a possible therapeutic approach in clinical practice. […] MERS-CoV structural and accessory proteins, including M, ORF4a, ORF4b, and ORF5 had all been proved that could antagonize IFN-I signaling and inhibit ISG productions.
  • #2 Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors in a Differential Mechanism
    https://www.jmb.or.kr/journal/view.html?doi=10.4014/jmb.1911.11024
    Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the beta coronavirus subfamily and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-) promoter activities. Here, we report that ORF8b seem to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. […] ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.
  • #2 Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220126
    Now emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. […] We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). […] MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans.
  • #2
    https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)
    Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by Middle East respiratory syndrome coronavirus (MERSCoV) that was first identified in Saudi Arabia in 2012. […] MERS-CoV is a zoonotic virus, meaning it is transmitted between animals and people. […] The clinical spectrum of MERS-CoV infection ranges from no symptoms (asymptomatic) or mild respiratory symptoms to severe acute respiratory disease and death. […] Severe illness can cause respiratory failure that requires mechanical ventilation or support in an intensive care unit. […] Human-to-human transmission is possible and has occurred predominantly among close contacts and in health care settings. […] Approximately 80% of human cases have been reported by Saudi Arabia, largely as a result of direct or indirect contact with infected dromedary camels or infected individuals in health care facilities.
  • #2 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/html
    The spike protein of MERS-CoV, which is responsible for MERS-CoV entry is considered as a key target for vaccine development against MERS-CoV infection. […] Neutralizing monoclonal antibodies bind to MERS-CoV spike protein and prevent virus-entry and following membrane fusion, therefore inhibit viral replication and reduce clinical diseases in animal models and humans.
  • #3 About Middle East Respiratory Syndrome (MERS) | MERS | CDC
    https://www.cdc.gov/mers/about/index.html
    Middle East Respiratory Syndrome (MERS) is a viral respiratory illness caused by a coronavirus called Middle East respiratory syndrome coronavirus (MERS-CoV. The virus can spread from camels to people through direct physical contact. Limited human-to-human transmission is possible. MERS has caused severe respiratory disease in most diagnosed cases, and many of those patients died. […] In most known MERS cases, the infected person developed pneumonia. Additional complications such as kidney failure have also occurred. About 3 or 4 out of every 10 people reported with a MERS infection died. […] The virus that causes MERS can spread through respiratory secretions, such as saliva or mucous, of infected animals or people. The MERS-CoV virus is mostly found in camels (dromedaries), and direct physical contact with camels can lead to transmission to humans. People infected through contact with camels can then spread the virus to other people. […] Researchers continue to investigate clusters of MERS cases to better understand how the virus spreads.
  • #3 Middle East respiratory syndrome coronavirus (MERS-CoV) internalization does not rely on DPP4 cytoplasmic tail signaling | npj Viruses
    https://www.nature.com/articles/s44298-024-00080-y
    Middle East respiratory syndrome coronavirus (MERS-CoV) infects respiratory epithelial cells in humans and camels by binding to dipeptidyl peptidase 4 (DPP4) as its entry receptor. DPP4 is a multifunctional type II membrane protein with a long ectodomain and a short six-amino-acid (aa) cytoplasmic tail. MERS-CoV is known to bind to the ectodomain of DPP4 to gain entry into the host cell. However, the role of the cytoplasmic tail in the entry process remains unclear. […] Overall, these data suggest that, although MERS-CoV binds to DPP4, other host factors may need to interact with DPP4 or the spike protein to trigger internalization. […] MERS-CoV uses dipeptidyl peptidase 4 (DPP4) as an entry receptor, which belongs to the serine peptidase family and is predominantly expressed in epithelial cells of the lungs, liver, kidney, intestine, thymocytes, and alveolar macrophages. The distribution of DPP4 in host cells plays a vital role in the transmission of MERS-CoV between camels and humans, as well as the severity of the infection. […] In contrast, the nasal cavity and small intestine of camels showed a high expression of DPP4, which has the potential to enhance the cross-species transmission of MERS-CoV.
  • #3 MERS infection route unlocked – News – Nature Middle East
    https://www.natureasia.com/en/nmiddleeast/article/10.1038/nmiddleeast.2014.250
    Typically, this involves cutting of the viral envelope protein at specific locations. This process is catalysed by specific protein-cutting enzymes called proteases, and prepares the envelope protein for fusion with the cell membrane. […] The researchers Jean Kaoru Millet and Gary Whittaker used bioinformatics combined with biochemical assays to examine the characteristics of the MERS-CoV spike protein, and found that fusion involves an unusual two-step mechanism. […] Both sites are recognized by a protease called furin, which acts on one during synthesis of the spike protein, and on the other later on, during entry into the host cell. […] Furin cleavage sites are observed in the S protein of MERS-CoV isolated from camels, says Whittaker. Acquisition of cleavage sites by mutation may have allowed the virus to infect more cell types within camels and to spread more easily through the animals’ secretions and fluids.
  • #3 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    Infection of epithelial cells with the MERS virus induce slow, but significant, IFN type I and II responses. […] With the present available knowledge, it is difficult to describe the exact pathogenesis of MERS-CoV, but it seems that viral replication in the macrophages results in extreme cytotoxicity and triggers the induction of pro-inflammatory chemicals which may lead to MERS-associated complications.
  • #3 Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis | Virology Journal | Full Text
    https://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0446-6
    Middle-East Respiratory Syndrome coronavirus (MERS-CoV) was identified to cause severe respiratory infection in humans since 2012. […] Currently, the pathogenesis of human MERS-CoV infection remains poorly understood. […] Human respiratory epithelial cells are highly susceptible to MERS-CoV and can support productive viral replication. […] However, the induction of antiviral cytokines and proinflammatory cytokines/chemokines are substantially dampened in the infected epithelial cells, due to the antagonistic mechanisms evolved by the virus. […] MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, triggering the aberrant production of proinflammatory cytokines/chemokines. […] MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells.
  • #3 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/17343
    Several factors could be involved in MERS pathogenesis, including viral and host factors, interferon induction, dysregulation of cytokines and adaptive immune responses. […] MERS-CoV could efficiently infect human dendritic cells and macrophages in vitro which would help the virus to dysregulate the immune system. […] MERS-CoV also has the ability to infect T cells through their highly expression of CD26, leading to T cell apoptosis, which might potentially disrupt anti-viral T cell responses. […] MERS-CoV replication is highly sensitive to type I interferon (IFN-I) treatment in cell culture suggesting that IFN-I treatment could be a possible therapeutic approach in clinical practice. […] MERS-CoV structural and accessory proteins, including M, ORF4a, ORF4b, and ORF5 had all been proved that could antagonize IFN-I signaling and inhibit ISG productions.
  • #3 Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors in a Differential Mechanism
    https://www.jmb.or.kr/journal/view.html?doi=10.4014/jmb.1911.11024
    Previously, we demonstrated that ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the IFN- signaling pathway. Interestingly, mechanisms of ORF8b-mediated inhibition seem to vary as protein levels of MDA5 were down-regulated by ORF8b while those of RIG-I were barely affected. […] These data suggest that ORF8b may differentially inhibit MDA5- or RIG-I-mediated induction of the IFN- pathway. […] ORF8b strongly inhibited both RIG-I-1-734- and RIG-I-1-228-mediated activation of the IFN- promoter activities. These data suggest that ORF8b may inhibit CARD-CARD interactions between RIG-I and MAVS. […] These data suggest that ORF8b-mediated inhibition of the IFN- signaling pathway does not involve direct inhibition of IRF3. Rather, it is likely that the target(s) of ORF8b is upstream of it.
  • #3 Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220126
    Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. […] Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition. […] Small animal models of emerging viral pathogenesis are fundamental tools to further our understanding of the molecular and genetic mechanisms driving severe disease outcomes after infection. […] Emerging viral pathogens like Ebola virus, yellow fever virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) are major threats to global public health.
  • #3 Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183850
    MERS-CoV is mainly spreading across the geographical region of the Middle East while only sporadic cases are reported in the Europe, North America, Africa, and lately Asia. […] The modes of MERS-CoV transmission by droplet, contact, or airborne are not yet confirmed as well and thus its transmission among animals and from animals to human and human to human remains unclear. […] The viral cytopathic effects clearly show prominent syncytium formation in humans as well as non-human primates. MERS-CoV targets directly the lower respiratory tract (pneumocytes) in dromedary camels and continues to replicate preferentially in the airway cells of the upper respiratory tract. […] The clinical manifestations of MERS-CoV infections represent a wide spectrum ranging from asymptomatic cases to the ones with severe respiratory indexes.
  • #3 Origins and pathogenesis of Middle East respiratory… | F1000Research
    https://f1000research.com/articles/6-1628
    Despite intensive research over the last five years, remarkably little is known about MERS-CoV pathogenesis. […] In the absence of robust post-mortem data from humans, numerous attempts have been made to establish non-human primate models that recapitulate severe human disease caused by MERS-CoV. […] The lone autopsy report, stemming from an April 2014 case in the United Arab Emirates, identifies type 2 alveolar pneumocytes and respiratory multinucleated syncytial cells of uncertain origin as the primary targets of MERS-CoV. […] Consistent with tropism for cells in the lower airway, the primary pathology observed was diffuse alveolar damage, and there was evidence for immune-mediated pathology in uninfected areas of the lung. […] MERS-CoV does not replicate in mice, because mouse DPP4 (mDPP4) does not support MERS-CoV entry, and this is due to two amino acid differences relative to human DPP4 in the region that interacts with Spike.
  • #3 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. […] A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. […] Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. […] MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. […] The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. […] The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). […] The DPP4 has been reported as a neutrophil chemo repellent; therefore, the variations in DPP4 shedding during MERS-CoV infection could influence the composition of the immune infiltrate, and ultimately to the outcome of the infection.
  • #3 SARS and MERS | BCM
    https://www.bcm.edu/departments/molecular-virology-and-microbiology/emerging-infections-and-biodefense/specific-agents/sars-mers
    However, the virus is not easily transmitted from person to person and there has been no sustained transmission of MERS-CoV. […] MERS-CoV has continued to spread as recently as 2020, albeit at very low rates, but the potential for a further outbreak remains. […] The MERS outbreak in 2015 provided a warning of how easily new diseases can be transported to other continents and spread before the disease is recognized. […] Texas Children’s CVD and their collaborators based their vaccine development on a segment of the SARS-CoV or MERS-CoV spike protein (a protein found on the outside of the virus that interacts with the host cell) known as the receptor binding domain (RBD). […] The idea is that the vaccines would stimulate neutralizing antibodies which would block the attachment of the virus to its receptor on the host cell, thus preventing infection by the coronaviruses. […] The researchers have shown that the RBD vaccine candidate does elicit a strong neutralizing antibody response and protects vaccinated animals against a challenge viral infection.
  • #3
    https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)
    Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by Middle East respiratory syndrome coronavirus (MERSCoV) that was first identified in Saudi Arabia in 2012. […] MERS-CoV is a zoonotic virus, meaning it is transmitted between animals and people. […] The clinical spectrum of MERS-CoV infection ranges from no symptoms (asymptomatic) or mild respiratory symptoms to severe acute respiratory disease and death. […] Severe illness can cause respiratory failure that requires mechanical ventilation or support in an intensive care unit. […] Human-to-human transmission is possible and has occurred predominantly among close contacts and in health care settings. […] Approximately 80% of human cases have been reported by Saudi Arabia, largely as a result of direct or indirect contact with infected dromedary camels or infected individuals in health care facilities.
  • #4 Middle East respiratory syndrome coronavirus (MERS-CoV) internalization does not rely on DPP4 cytoplasmic tail signaling | npj Viruses
    https://www.nature.com/articles/s44298-024-00080-y
    Middle East respiratory syndrome coronavirus (MERS-CoV) infects respiratory epithelial cells in humans and camels by binding to dipeptidyl peptidase 4 (DPP4) as its entry receptor. DPP4 is a multifunctional type II membrane protein with a long ectodomain and a short six-amino-acid (aa) cytoplasmic tail. MERS-CoV is known to bind to the ectodomain of DPP4 to gain entry into the host cell. However, the role of the cytoplasmic tail in the entry process remains unclear. […] Overall, these data suggest that, although MERS-CoV binds to DPP4, other host factors may need to interact with DPP4 or the spike protein to trigger internalization. […] MERS-CoV uses dipeptidyl peptidase 4 (DPP4) as an entry receptor, which belongs to the serine peptidase family and is predominantly expressed in epithelial cells of the lungs, liver, kidney, intestine, thymocytes, and alveolar macrophages. The distribution of DPP4 in host cells plays a vital role in the transmission of MERS-CoV between camels and humans, as well as the severity of the infection. […] In contrast, the nasal cavity and small intestine of camels showed a high expression of DPP4, which has the potential to enhance the cross-species transmission of MERS-CoV.
  • #4 Middle East respiratory syndrome coronavirus (MERS-CoV) internalization does not rely on DPP4 cytoplasmic tail signaling | npj Viruses
    https://www.nature.com/articles/s44298-024-00080-y
    The infection cycle of coronaviruses begins with the binding of virus spike glycoprotein to the receptor on the host cell surface, which triggers receptor signaling and allows the virus to internalize and enter the cells. […] However, despite molecular and structural insights into MERS-CoV and the role and involvement of other host factors in entry, understanding of how DPP4 signaling pathways actively drive virus/receptor complex internalization is limited. MERS-CoV internalization might be triggered by DPP4 alone or along with other host factors such as sialic acid, tetraspanin, host proteases TMPRSS2, or other unknown host factor(s) to contribute to virus internalization. […] In this study, we showed that the DPP4 cytoplasmic tail is not crucial for MERS-CoV internalization. Our initial findings demonstrate that MERS-CoV can enter cells via direct membrane fusion and endocytosis. […] These findings demonstrate that the absence of the cytoplasmic tail, DPP4 presented on the cell membrane, allows for the binding of the MERS-CoV spike protein and its subsequent internalization into host cells. Therefore, we speculate that MERS-CoV binds to DPP4, and following receptor binding, another host protein may trigger its internalization process.
  • #4 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    Before the discovery of MERS-CoV, SARS-CoV was considered the most pathogenic coronavirus. However, the higher pathogenicity of MERS-CoV was apparent by the higher number of deaths caused by this virus. […] MERS-CoV can also induce pro-inflammatory cytokines but lacks in production of innate antiviral cytokines compared with SARS-CoV. Suggesting MERS-CoV induces delayed pro-inflammatory response and attenuates innate immunity, which suggests that MERS-CoV is more lethal compared with SARS-CoV. […] Primarily the MERS virus interacts with the host DPP4 receptor through its spike (S) protein after entering the respiratory tract. DPP4 receptors are present on the epithelial surface of various human organs such as, the lungs, kidneys, liver, bone marrow, thymus and intestines. […] Recent findings have suggested that a prior existing pulmonary ailment might increase the chances of such individuals contracting MERS, as chronic pulmonary diseases results in enhanced DPP4 expression.
  • #4 Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors in a Differential Mechanism
    https://www.jmb.or.kr/journal/view.html?doi=10.4014/jmb.1911.11024
    Taken together, here we report that ORF8b, encoded by MERS-CoV, is a strong antagonist of the RLR signaling pathway. ORF8b significantly down-regulated both MDA5-and RIG-I-mediated induction of IFN- promoter activities. Interestingly, ORF8b inhibited all forms of RIG-I (full-length, RIG-I-1-734 and RIG-I-1-228), implying that it may inhibit CARD-CARD interactions between RIG-I and MAVS without affecting protein levels of RIG-I, leading to lower levels of IRF3 phosphorylation.
  • #4 Origins and pathogenesis of Middle East respiratory… | F1000Research
    https://f1000research.com/articles/6-1628
    Despite intensive research over the last five years, remarkably little is known about MERS-CoV pathogenesis. […] In the absence of robust post-mortem data from humans, numerous attempts have been made to establish non-human primate models that recapitulate severe human disease caused by MERS-CoV. […] The lone autopsy report, stemming from an April 2014 case in the United Arab Emirates, identifies type 2 alveolar pneumocytes and respiratory multinucleated syncytial cells of uncertain origin as the primary targets of MERS-CoV. […] Consistent with tropism for cells in the lower airway, the primary pathology observed was diffuse alveolar damage, and there was evidence for immune-mediated pathology in uninfected areas of the lung. […] MERS-CoV does not replicate in mice, because mouse DPP4 (mDPP4) does not support MERS-CoV entry, and this is due to two amino acid differences relative to human DPP4 in the region that interacts with Spike.
  • #4 Host Determinants of MERS-CoV Transmission and Pathogenesis
    https://www.mdpi.com/1999-4915/11/3/280
    This review highlights the role of some MERS-CoV-interacting host factors—especially DPP4—in MERS-CoV pathogenesis and transmission. […] MERS-CoV infection in these animals merely causes mild upper respiratory tract infection, but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species. […] Although the clinical manifestations, as well as transmission, are remarkably different in MERS-CoV-infected humans and dromedary camels, the viruses isolated from these two species are highly similar, if not indistinguishable. […] This indicates that host factors play a significant role in MERS-CoV pathogenesis and transmission. […] DPP4 is the functional receptor of MERS-CoV; its absence renders cells resistant to this virus, while its transient expression in non-susceptible cells permits viral replication.
  • #4 MERS-related coronavirus – Wikipedia
    https://en.wikipedia.org/wiki/MERS-related_coronavirus
    Middle East respiratory syndromerelated coronavirus (MERS-CoV) is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the DPP4 receptor. […] MERS-CoV is one of seven known coronaviruses to infect humans, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, the original SARS-CoV (or SARS-CoV-1), and SARS-CoV-2. It has frequently been referred to as a SARS-like virus. […] In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells, and it has been shown to effectively evade the innate immune responses and antagonize interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells.
  • #4 About Middle East Respiratory Syndrome (MERS) | MERS | CDC
    https://www.cdc.gov/mers/about/index.html
    Middle East Respiratory Syndrome (MERS) is a viral respiratory illness caused by a coronavirus called Middle East respiratory syndrome coronavirus (MERS-CoV. The virus can spread from camels to people through direct physical contact. Limited human-to-human transmission is possible. MERS has caused severe respiratory disease in most diagnosed cases, and many of those patients died. […] In most known MERS cases, the infected person developed pneumonia. Additional complications such as kidney failure have also occurred. About 3 or 4 out of every 10 people reported with a MERS infection died. […] The virus that causes MERS can spread through respiratory secretions, such as saliva or mucous, of infected animals or people. The MERS-CoV virus is mostly found in camels (dromedaries), and direct physical contact with camels can lead to transmission to humans. People infected through contact with camels can then spread the virus to other people. […] Researchers continue to investigate clusters of MERS cases to better understand how the virus spreads.
  • #4 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. […] A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. […] Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. […] MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. […] The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. […] The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). […] The DPP4 has been reported as a neutrophil chemo repellent; therefore, the variations in DPP4 shedding during MERS-CoV infection could influence the composition of the immune infiltrate, and ultimately to the outcome of the infection.
  • #4 Current understanding of middle east respiratory syndrome coronavirus infection in human and animal models – Wang – Journal of Thoracic Disease
    https://jtd.amegroups.org/article/view/20125/17343
    Several factors could be involved in MERS pathogenesis, including viral and host factors, interferon induction, dysregulation of cytokines and adaptive immune responses. […] MERS-CoV could efficiently infect human dendritic cells and macrophages in vitro which would help the virus to dysregulate the immune system. […] MERS-CoV also has the ability to infect T cells through their highly expression of CD26, leading to T cell apoptosis, which might potentially disrupt anti-viral T cell responses. […] MERS-CoV replication is highly sensitive to type I interferon (IFN-I) treatment in cell culture suggesting that IFN-I treatment could be a possible therapeutic approach in clinical practice. […] MERS-CoV structural and accessory proteins, including M, ORF4a, ORF4b, and ORF5 had all been proved that could antagonize IFN-I signaling and inhibit ISG productions.
  • #4 MERS – Wikipedia
    https://en.wikipedia.org/wiki/MERS
    Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by Middle East respiratory syndrome-related coronavirus (MERS-CoV). Symptoms may range from none, to mild, to severe depending on age and risk level. Typical symptoms include fever, cough, diarrhea, and shortness of breath. The disease is typically more severe in those with other health problems. […] MERS-CoV is a virus in the coronavirus family believed to be originally from bats. However, humans are typically infected from camels, either during direct contact or indirectly through respiratory droplets. Spread between humans typically requires close contact with an infected person. Its spread is uncommon outside of hospitals. […] While the mechanism of spread of MERS-CoV is currently not known, based on experience with prior coronaviruses, such as SARS, the WHO currently recommends that all individuals coming into contact with MERS suspects should (in addition to standard precautions): Wear a medical mask, Wear eye protection (i.e. goggles or a face shield), Wear a clean, non sterile, long sleeved gown; and gloves (some procedures may require sterile gloves). […] It is believed that the existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection.
  • #5 Origins and pathogenesis of Middle East respiratory… | F1000Research
    https://f1000research.com/articles/6-1628
    Despite intensive research over the last five years, remarkably little is known about MERS-CoV pathogenesis. […] In the absence of robust post-mortem data from humans, numerous attempts have been made to establish non-human primate models that recapitulate severe human disease caused by MERS-CoV. […] The lone autopsy report, stemming from an April 2014 case in the United Arab Emirates, identifies type 2 alveolar pneumocytes and respiratory multinucleated syncytial cells of uncertain origin as the primary targets of MERS-CoV. […] Consistent with tropism for cells in the lower airway, the primary pathology observed was diffuse alveolar damage, and there was evidence for immune-mediated pathology in uninfected areas of the lung. […] MERS-CoV does not replicate in mice, because mouse DPP4 (mDPP4) does not support MERS-CoV entry, and this is due to two amino acid differences relative to human DPP4 in the region that interacts with Spike.
  • #5 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    MERS-CoV has been reported to elicit attenuated innate immune responses with delayed proinflammatory cytokine induction in in vitro and in vivo, which might lead to immune dysfunctions. […] MERS-CoV has been reported to induce greater dysregulation of the host response to infection than SARS-CoV. […] The decreased expression of IFN-, retinoic inducible acid gene (RIG)-1, melanoma differentiation associate (MDA5), and IFN regulatory factors IRF-3 and IRF-7 have been reported in bronchoalveolar lavage (BAL) and serum of patients in advanced stages of MERS. […] The involvement of pattern recognition receptors and downstream signaling at the cellular level is required to understand the molecular pathogenesis of MERS-CoV. […] The role of accessory proteins of MERS-CoV should be dissected out to understand their diverse roles in the immune evasion strategies adopted by MERS-CoV to inhibit IFN- expression.
  • #5 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    CoV nsp1 is a serious virulence factor, which facilitates the biological actions of MERS-CoV. Studying the nsp1 can advance our understanding of pathogenicity of MERS-CoV and facilitate development of better therapeutics. Host gene expression in infected cells is suppressed by MERS-CoV nsp1, which also promotes virus assembly or budding in in vitro, leading to efficient virus replication, suggesting nsp1 is also critical for MERS-CoV replication and promotes production of virus particles in the host. […] The infection with MERS-CoV of human epithelial cells induces the release of pro-inflammatory chemokines and cytokines from the monocyte-derived macrophages. It is believed that these chemokines/cytokines cause inflammatory changes and tissue injury through infiltration of immune cells in the lower respiratory tract. […] Thus, these phagocytes act like reservoirs and means of transportation for these viruses, helping to replicate and disseminate, such as the HIV virus.
  • #5 SARS and MERS: recent insights into emerging coronaviruses | Nature Reviews Microbiology
    https://www.nature.com/articles/nrmicro.2016.81
    SARS-CoV and MERS-CoV use several strategies to avoid the innate immune response. […] The pathogenesis of MERS-CoV in dromedary camels has been studied experimentally in a limited number of animals. These animals developed transient mild disease; however, large quantities of MERS-CoV were shed from the upper respiratory tract, in line with the predominant replication of MERS-CoV in the nasal turbinates and larynx in these animals, which explains the frequent zoonotic transmission.
  • #5 Azthena logo with the word Azthena
    https://www.news-medical.net/health/Middle-East-Respiratory-Syndrome-Coronavirus-(MERS-CoV)-Symptoms.aspx
    MERS-CoV belongs to a family of enveloped, large, single-stranded RNA viruses known as Coronaviridae. The virus enters the human body through a common receptor, dipeptidyl peptidase 4 (also known as CD26), and subsequently replicates in bronchial, bronchiolar and alveolar epithelial cells. MERS-CoV has been detected primarily in respiratory secretions, with the viral load being highest in the lower parts of the respiratory tract. […] Compared with another member of this viral family known as severe acute respiratory syndrome coronavirus (SARS-CoV), MERS-CoV has the propensity to establish a productive infection in macrophages and dendritic cells. This can in turn instigate the release of proinflammatory cytokines, resulting in protracted inflammation and tissue damage that clinically manifests as a severe form of pneumonia and respiratory failure.
  • #5
    https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)
    No vaccine or specific treatment are currently available, however several MERS-CoV specific vaccines and treatments are in clinical development. […] Transmission of MERS-CoV has occurred in health care facilities in several Member States, including from patients to health care workers and between patients in a health care setting before MERS-CoV was diagnosed. […] Infection prevention and control measures are therefore critical to prevent the possible spread of MERSCoV in health care facilities. […] WHO continues to work with public health and animal health specialists, clinicians and scientists in affected and at-risk Member States to gather and share scientific evidence to better understand the virus and the disease it causes.
  • #6 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    CoV nsp1 is a serious virulence factor, which facilitates the biological actions of MERS-CoV. Studying the nsp1 can advance our understanding of pathogenicity of MERS-CoV and facilitate development of better therapeutics. Host gene expression in infected cells is suppressed by MERS-CoV nsp1, which also promotes virus assembly or budding in in vitro, leading to efficient virus replication, suggesting nsp1 is also critical for MERS-CoV replication and promotes production of virus particles in the host. […] The infection with MERS-CoV of human epithelial cells induces the release of pro-inflammatory chemokines and cytokines from the monocyte-derived macrophages. It is believed that these chemokines/cytokines cause inflammatory changes and tissue injury through infiltration of immune cells in the lower respiratory tract. […] Thus, these phagocytes act like reservoirs and means of transportation for these viruses, helping to replicate and disseminate, such as the HIV virus.
  • #6 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    MERS-CoV has been reported to elicit attenuated innate immune responses with delayed proinflammatory cytokine induction in in vitro and in vivo, which might lead to immune dysfunctions. […] MERS-CoV has been reported to induce greater dysregulation of the host response to infection than SARS-CoV. […] The decreased expression of IFN-, retinoic inducible acid gene (RIG)-1, melanoma differentiation associate (MDA5), and IFN regulatory factors IRF-3 and IRF-7 have been reported in bronchoalveolar lavage (BAL) and serum of patients in advanced stages of MERS. […] The involvement of pattern recognition receptors and downstream signaling at the cellular level is required to understand the molecular pathogenesis of MERS-CoV. […] The role of accessory proteins of MERS-CoV should be dissected out to understand their diverse roles in the immune evasion strategies adopted by MERS-CoV to inhibit IFN- expression.
  • #6 Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183850
    MERS-CoV is mainly spreading across the geographical region of the Middle East while only sporadic cases are reported in the Europe, North America, Africa, and lately Asia. […] The modes of MERS-CoV transmission by droplet, contact, or airborne are not yet confirmed as well and thus its transmission among animals and from animals to human and human to human remains unclear. […] The viral cytopathic effects clearly show prominent syncytium formation in humans as well as non-human primates. MERS-CoV targets directly the lower respiratory tract (pneumocytes) in dromedary camels and continues to replicate preferentially in the airway cells of the upper respiratory tract. […] The clinical manifestations of MERS-CoV infections represent a wide spectrum ranging from asymptomatic cases to the ones with severe respiratory indexes.
  • #6 Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis | Virology Journal | Full Text
    https://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0446-6
    Although data from clinical, in vitro and ex vivo studies suggested the potential for virus dissemination, extrapulmonary involvement in MERS patients has not been ascertained due to the lack of autopsy study. […] More research findings on the pathogenesis of MERS and the tissue tropisms of MERS-CoV may help to improve the treatment and infection control of MERS. […] The pathogenesis of human MERS-CoV infection remains poorly understood. […] However, MERS-CoV has evolved multiple antagonistic mechanisms to attenuate the induction of antiviral and proinflammatory cytokines in the affected epithelial cells. […] Additionally, MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, which elicits the aberrant production of proinflammatory cytokines/chemokines. […] MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells. […] More studies are warranted to further characterize the tissue tropisms of MERS-CoV for the better understanding towards the pathogenesis of MERS.
  • #6
    https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)
    No vaccine or specific treatment are currently available, however several MERS-CoV specific vaccines and treatments are in clinical development. […] Transmission of MERS-CoV has occurred in health care facilities in several Member States, including from patients to health care workers and between patients in a health care setting before MERS-CoV was diagnosed. […] Infection prevention and control measures are therefore critical to prevent the possible spread of MERSCoV in health care facilities. […] WHO continues to work with public health and animal health specialists, clinicians and scientists in affected and at-risk Member States to gather and share scientific evidence to better understand the virus and the disease it causes.
  • #7 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    Infection of epithelial cells with the MERS virus induce slow, but significant, IFN type I and II responses. […] With the present available knowledge, it is difficult to describe the exact pathogenesis of MERS-CoV, but it seems that viral replication in the macrophages results in extreme cytotoxicity and triggers the induction of pro-inflammatory chemicals which may lead to MERS-associated complications.
  • #7 Factsheet about Middle East respiratory syndrome coronavirus (MERS-CoV)
    https://www.ecdc.europa.eu/en/middle-east-respiratory-syndrome-coronavirus/factsheet
    The hypothesis that dromedary camels are hosts of MERS CoV has been proven by the viral RNA detection in different specimens collected from these animals in Qatar, Saudi Arabia, Oman and Egypt and the isolation of the virus from nasal and faecal samples. […] The exact routes of transmission among camels and from camels to humans are still not clear. […] MERS-CoV survived better than A(H1N1) viruses on inanimate surfaces and it has the ability to remain viable in aerosol. […] MERS-CoV virus can be detected with higher viral load and longer duration in the lower respiratory tract than in the upper respiratory tract, and has been detected also in faeces, serum, urine and blood samples.
  • #8 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. […] A large amount of information is now available regarding the virus, its structure, route of transmission and its pathophysiology. Therefore, this review summarizes the current understanding of MERS-CoV’s pathogenesis, treatment options and recent scientific advancements in vaccine and other therapeutic developments, and the major steps taken for MERS prevention control. […] Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a zoonotic virus, whose mode of transmission is from animals to humans. The origin of the virus is believed to be bats, from which it was then transferred to camels. Camels are currently regarded as a major host for MERS-CoV. […] The pathogenic agent of Middle East respiratory syndrome is a new coronavirus which was initially identified from the respiratory content of a patient who was infected, and died, as a result of infection from a mysterious viral disease showing pneumonia like symptoms in Saudi Arabia in 2012. […] The understanding of MERS-CoV pathogenesis has been limited due to nonavailability of patient autopsy or pathological samples from the patients. Our understanding of the disease pathogenesis is based entirely on in vitro studies. […] The severity of MERS-CoV infection is relatively more in patients with co-morbid conditions, such as chronic lung disease, renal failure, diabetes and others with compromised immune systems.
  • #8 Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220126
    In this study, we characterized the daily variation of different peripheral blood cell populations in a mouse model of MERS-CoV infection and pathogenesis until 4 days post infection (dpi). […] Importantly, we demonstrated that the disease severity could be differentiated by CBC performed daily in a longitudinal study of mice infected with either a sublethal or lethal dose of MERS-CoV. […] Therefore, neutrophils in peripheral blood prior to the onset of severe clinical disease may serve as a predictive biomarker of severe MERS-CoV disease in mice, just as elevated neutrophils at the time of SARS-CoV patient admission predicted adverse outcomes in humans. […] The studies described herein highlight the predictive value and clinical translatability of the CBC in the study of emerging virus pathogenesis.
  • #8 Factsheet about Middle East respiratory syndrome coronavirus (MERS-CoV)
    https://www.ecdc.europa.eu/en/middle-east-respiratory-syndrome-coronavirus/factsheet
    The hypothesis that dromedary camels are hosts of MERS CoV has been proven by the viral RNA detection in different specimens collected from these animals in Qatar, Saudi Arabia, Oman and Egypt and the isolation of the virus from nasal and faecal samples. […] The exact routes of transmission among camels and from camels to humans are still not clear. […] MERS-CoV survived better than A(H1N1) viruses on inanimate surfaces and it has the ability to remain viable in aerosol. […] MERS-CoV virus can be detected with higher viral load and longer duration in the lower respiratory tract than in the upper respiratory tract, and has been detected also in faeces, serum, urine and blood samples.
  • #9 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    Before the discovery of MERS-CoV, SARS-CoV was considered the most pathogenic coronavirus. However, the higher pathogenicity of MERS-CoV was apparent by the higher number of deaths caused by this virus. […] MERS-CoV can also induce pro-inflammatory cytokines but lacks in production of innate antiviral cytokines compared with SARS-CoV. Suggesting MERS-CoV induces delayed pro-inflammatory response and attenuates innate immunity, which suggests that MERS-CoV is more lethal compared with SARS-CoV. […] Primarily the MERS virus interacts with the host DPP4 receptor through its spike (S) protein after entering the respiratory tract. DPP4 receptors are present on the epithelial surface of various human organs such as, the lungs, kidneys, liver, bone marrow, thymus and intestines. […] Recent findings have suggested that a prior existing pulmonary ailment might increase the chances of such individuals contracting MERS, as chronic pulmonary diseases results in enhanced DPP4 expression.
  • #9 Middle East respiratory syndrome: pathogenesis and therapeutic developments
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7080179/
    The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. […] A large amount of information is now available regarding the virus, its structure, route of transmission and its pathophysiology. Therefore, this review summarizes the current understanding of MERS-CoV’s pathogenesis, treatment options and recent scientific advancements in vaccine and other therapeutic developments, and the major steps taken for MERS prevention control. […] Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a zoonotic virus, whose mode of transmission is from animals to humans. The origin of the virus is believed to be bats, from which it was then transferred to camels. Camels are currently regarded as a major host for MERS-CoV. […] The pathogenic agent of Middle East respiratory syndrome is a new coronavirus which was initially identified from the respiratory content of a patient who was infected, and died, as a result of infection from a mysterious viral disease showing pneumonia like symptoms in Saudi Arabia in 2012. […] The understanding of MERS-CoV pathogenesis has been limited due to nonavailability of patient autopsy or pathological samples from the patients. Our understanding of the disease pathogenesis is based entirely on in vitro studies. […] The severity of MERS-CoV infection is relatively more in patients with co-morbid conditions, such as chronic lung disease, renal failure, diabetes and others with compromised immune systems.
  • #9 Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220126
    Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. […] Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition. […] Small animal models of emerging viral pathogenesis are fundamental tools to further our understanding of the molecular and genetic mechanisms driving severe disease outcomes after infection. […] Emerging viral pathogens like Ebola virus, yellow fever virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) are major threats to global public health.
  • #10 Host Determinants of MERS-CoV Transmission and Pathogenesis
    https://www.mdpi.com/1999-4915/11/3/280
    These data illustrate that DPP4 has the capacity to determine the host range of MERS-CoV. […] The preference of MERS-CoV to use certain host proteases is influenced by the type of target cell and the cleavage stage of their S protein prior to infection. […] The differential expression of host factors that limits the infection should also be taken into account. […] DPP4 upregulation in type I pneumocytes and insufficient type I interferon response might be crucial determinants for severe MERS-CoV infection. […] Further investigation of the host determinants of MERS-CoV pathogenesis may offer insights for developing novel therapeutic measures.
  • #11 Middle East Respiratory Syndrome Virus Pathogenesis
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7171719/
    Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and humans. […] A decade later (June 2012), another novel CoV was implicated as the cause of Middle East respiratory syndrome (MERS) in Saudi Arabia. […] Severe lines of evidence suggest that dromedary camels have been the major cause of transmission to humans. […] MERS-CoV causes an acute, highly lethal pneumonia and renal dysfunction. […] The major complications reported in fatal cases are hyperkalemia with associated ventricular tachycardia, disseminated intravascular coagulation, pericarditis, and multiorgan failure. […] The case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV (9.6%). […] The DPP4 has been reported as a neutrophil chemo repellent; therefore, the variations in DPP4 shedding during MERS-CoV infection could influence the composition of the immune infiltrate, and ultimately to the outcome of the infection.

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