Orf, choroba zwana również pęcherzycą zakaźną, dermatitis pęcherzycową lub ecthyma contagiosum
Patofizjologia i mechanizm

Orf, znany również jako pęcherzyca zakaźna, jest wirusową chorobą skóry wywołaną przez Parapoxvirus z rodziny Orfviridae, naturalnie występującą u młodych owiec i kóz. Zakażenie u ludzi następuje przez kontakt z zakażonymi zwierzętami lub skażonymi materiałami. Wirus o wymiarach 260 x 160 nm replikuje się w komórkach warstwy zastępczej naskórka pochodzących ze ścian mieszków włosowych, powodując zmiany skórne takie jak pęcherzyki, grudki i strupy, głównie na granicy śluzówkowo-skórnej warg i wokół siekaczy. Patogeneza obejmuje odpowiedź komórkową z martwicą i złuszczaniem naskórka oraz proliferację naczyń włosowatych, co sprzyja replikacji wirusa i gojeniu ran. Wirus wykorzystuje makroautofagię i indukuje złożoną odpowiedź cytokinową, początkowo Th1, a następnie Th2, co umożliwia mu unikanie układu odpornościowego gospodarza.

  1. Definicja Orf
  2. Patogeneza zakażenia Orf
    1. Mechanizm infekcji
    2. Molekularne mechanizmy patogenności
  3. Czynniki wirulencji wirusa Orf
    1. Główne białka wirulencji
    2. Modulacja odpowiedzi immunologicznej gospodarza
  4. Konsekwencje patologiczne zakażenia Orf
    1. Zmiany w tkankach gospodarza
    2. Odpowiedź immunologiczna na zakażenie
  5. Potencjał terapeutyczny i immunomodulacyjny
  6. Podsumowanie mechanizmów patogenezy Orf
    1. Kolejne rozdziały

Definicja Orf

Orf, choroba zwana również pęcherzycą zakaźną, dermatitis pęcherzycową lub ecthyma contagiosum, jest chorobą wirusową skóry spowodowaną przez wirus z rodzaju Parapoxvirus, należący do rodziny Orfviridae. Jest to choroba odzwierzęca występująca głównie u młodych owiec i kóz, które stanowią jej naturalnych gospodarzy. Choroba może być przenoszona na ludzi poprzez bezpośredni kontakt z zakażonymi zwierzętami, ich tuszami lub skażonymi materiałami nieożywionymi.123

Wirus Orf ma kształt cylindryczny, mierzy 260 x 160 nm, a jego powierzchniowe tubule tworzą długi układ krzyżowy, który jest widoczny w mikroskopie elektronowym przy barwieniu negatywnym. Genom wirusa zawiera 132 geny.45

Patogeneza zakażenia Orf

Mechanizm infekcji

Uszkodzenie skóry jest niezbędne do powstania zakażenia wirusem Orf i rozwoju typowych zmian. Analiza patogenezy eksperymentalnych zmian wywołanych przez kontakt wirusa z delikatnie uszkodzoną skórą wykazała, że wirus nie rozwija się w uszkodzonym naskórku, ale replikuje się w komórkach warstwy zastępczej naskórka, pochodzących ze ścian mieszków włosowych.6

Reakcja skórna składa się z odpowiedzi komórkowej z martwicą i złuszczaniem zmienionego naskórka i leżącej pod nim warstwy brodawkowatej skóry właściwej. Proces gojenia kończy się wytworzeniem trzeciego naskórka pochodzącego z głębszych części mieszków włosowych.7

Pierwotna zmiana wywołana przez Orf rozwija się na granicy śluzówkowo-skórnej warg i wokół wyrzynających się siekaczy, a może rozprzestrzeniać się na błonę śluzową jamy ustnej.8

Molekularne mechanizmy patogenności

Wirus Orf wykorzystuje różnorodne efekty immunomodulacyjne, aby uniknąć działania układu odpornościowego i zainfekować keratynocyty. Badania wykazały, że wirus wykorzystuje makroautofagię u ssaków, co potencjalnie przyczynia się do infekcji wirusowej i patogenezy u ludzi.9

ORFV koduje czynniki zjadliwości i immunomodulacyjne, które zakłócają działanie zapalnego mechanizmu obronnego gospodarza i przeciwwirusowe mechanizmy odpornościowe. Indukuje przejściową i złożoną odpowiedź cytokinową, początkowo reprezentowaną przez cytokiny związane z Th1, a następnie cytokiny związane z Th2.10

Czynniki wirulencji wirusa Orf

Główne białka wirulencji

Wirus Orf wykształcił wiele czynników zjadliwości, które działają samodzielnie lub koordynują się ze sobą, pomagając wirusowi w unikaniu odpowiedzi immunologicznej i zakażeniu gospodarza. Główne geny wirulencji zlokalizowane w regionach ITR (terminal inverted repeats) obejmują:11

  • Homolog owczego genu kodującego cytokinę IL-10 (vIL-10) – hamuje dojrzewanie i funkcję komórek prezentujących antygen (APC), takich jak komórki dendrytyczne, co prowadzi do zahamowania proliferacji i transkrypcji cytokin komórek Th112
  • Gen oporności na interferon (OVIFNR) – koduje białko, które wiąże się z wirusowym DNA dwuniciowym, hamuje aktywację kinazy białkowej (PKR) i zapobiega zmniejszeniu transkrypcji wirusowego mRNA13
  • Czynnik wzrostu śródbłonka naczyniowego (VEGF) – zwiększa proliferację komórek śródbłonka i zwiększa przepuszczalność naczyń, co sprzyja replikacji wirusa i tworzeniu krost14
  • Wirusowe białko wiążące chemokinę (vCBP) – białko o strukturze heksagonalnej, które wiąże receptory jako konkurencyjne inhibitory homologicznych cytokin i hamuje zapalenie15
  • Ankiryna (ANK) – grupa 5 białek, które degradują czynniki przeciwwirusowe gospodarza poprzez domeny podobne do F-box, promując replikację ORFV i zakażenie różnych gatunków16
  • Pirofosforylaza dUTP (dUTPase) – grupuje się z odpowiednikami ssaków i jest bardziej podobna do dUTPaz ssaków niż do dUTPaz innych pokswirusów17
  • Czynnik hamujący czynnik stymulujący tworzenie kolonii granulocytów-makrofagów (GIF) – specyficznie hamuje aktywność biologiczną IL-2 i GM-CSF18
  • ORFV121 – koduje nowy inhibitor NF-κB, który wiąże się z NF-κB i hamuje fosforylację i translokację jądrową NF-κB-p65, hamując tym samym translację genów związanych z odpowiedzią immunologiczną1920

Modulacja odpowiedzi immunologicznej gospodarza

Wirus Orf rozwija szereg strategii regulacji immunologicznej w celu replikacji i unikania odpowiedzi immunologicznej. Do głównych mechanizmów należą:21

  • Zakłócanie szlaku NF-κB – białka ORFV002, ORFV024 i ORFV121 zakłócają aktywację szlaku NF-κB, hamując fosforylację kompleksu IKK, co wpływa na fosforylację NF-κB-p65 i hamuje wydzielanie ważnych cytokin przez komórki odpornościowe gospodarza2223
  • Indukcja apoptozy – ORFV wywołuje apoptozę w komórkach APC, komórkach naskórka i komórkach limfatycznych, mediowaną przez szlak CD95. Niektóre białka błonowe ORFV indukują apoptozę w komórkach APC gospodarza i hamują aktywację limfocytów T poprzez szlak CD95/CD95L24
  • Hamowanie działania interferonu – białko kodowane przez gen oporności na interferon (OVIFNR) wiąże się z wirusowym DNA dwuniciowym, hamując aktywację kinazy białkowej zależnej od interferonu (PKR)25

Konsekwencje patologiczne zakażenia Orf

Zmiany w tkankach gospodarza

Zakażenie wirusem Orf stymuluje hiperplazję komórek naskórka i wzrost naczyń włosowatych ze zwiększoną przepuszczalnością naczyń, co pozwala na zwiększoną replikację wirusa i tworzenie strupów podczas gojenia ran.26

U owiec i kóz typowa zmiana charakteryzuje się pęcherzykami, grudkami i strupami na granicy skórno-śluzówkowej warg. U ludzi zmiany są zwykle ograniczone do rąk i twarzy, mają charakter bardziej proliferacyjny i mogą być bardzo uciążliwe.27

Odpowiedź immunologiczna na zakażenie

Wirus Orf wywołuje silną odpowiedź immunologiczną, która jest jednak skutecznie modulowana przez różne białka wirusa. Owce, które wyzdrowiały z naturalnego zakażenia, są wysoce odporne na ponowne zakażenie, co wskazuje na rozwój skutecznej odporności.28

ORFV może szybko pośredniczyć w odpowiedzi humoralnej i adaptacyjnej odporności. Pomimo tego, wirus rozwinął kilka mechanizmów umożliwiających przetrwanie w obecności układu odpornościowego, co skutkuje ponownymi zakażeniami.29

Potencjał terapeutyczny i immunomodulacyjny

Wirus Orf wykazuje działanie immunomodulacyjne i przeciwwirusowe, w tym działanie przeciwzwłóknieniowe, co zaobserwowano w próbkach wątroby szczurów zakażonych wirusem zapalenia wątroby typu B i wirusem zapalenia wątroby typu C.30

Wirus Orf jest szeroko uznawany za posiadający silną funkcję immunoregulacyjną u gospodarza. ORFV i niektóre kodowane przez niego białka mają dobre właściwości immunomodulacyjne, co może być wykorzystane w terapeutach.31

Podsumowanie mechanizmów patogenezy Orf

Patogeneza zakażenia wirusem Orf polega na złożonej interakcji między wirusem a układem odpornościowym gospodarza. Wirus wykorzystuje uszkodzenia skóry do wniknięcia, replikuje się w komórkach warstwy zastępczej naskórka i wykorzystuje szereg białek immunomodulacyjnych, aby uniknąć odpowiedzi immunologicznej. Powoduje to typowe zmiany skórne charakteryzujące się pęcherzykami, grudkami i strupami.3233

Wirus Orf rozwinął złożone mechanizmy molekularne umożliwiające mu przetrwanie w obecności układu odpornościowego gospodarza. Mechanizmy te obejmują hamowanie szlaku NF-κB, modulację odpowiedzi interferonowej, indukcję apoptozy w komórkach układu odpornościowego i produkcję białek wiążących chemokiny. Te strategie unikania odpowiedzi immunologicznej przyczyniają się do zdolności wirusa do wywoływania choroby i możliwości ponownych zakażeń.343536

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

  1. 10.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Orf Viral Infection – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK562191/
    Orf viral infection, also known as ecthyma contagiosum or contagious pustular dermatitis, is an occupational disease primarily acquired from infected sheep and goats. […] Orf is caused by the parapoxvirus Orfviridae. The orf virus plagues young sheep and goats, which are their natural host range. […] The orf virus uses various immunomodulatory effects to evade the immune system and infect keratinocytes. […] Further research findings have demonstrated that the orf virus uses macroautophagy in mammals, possibly contributing to the viral infection and pathogenesis in human hosts. […] The orf virus demonstrates immunomodulatory and antiviral activity, including antifibrotic activity, as observed in hepatic samples from rats infected with hepatitis B virus and hepatitis C virus. […] The infection caused by the orf virus is endemic to sheep and goats. Direct contact with active lesions from affected animals or contact with fomites can infect humans. […] Orf virus is rarely, if ever, transmitted from humans to other humans.
  • #2 Orf: Practice Essentials, Pathophysiology, Epidemiology
    https://emedicine.medscape.com/article/1133450-overview
    Orf is caused by infection with the orf virus that belongs to the Parapoxvirus genus, which also includes the milker’s nodule virus. […] The orf virus is able to produce a homolog of anti-inflammatory cytokine, interleukin (IL)10, which contributes to localized suppression of immunity. […] Orf is transmitted by direct contact inoculation usually via a wound in the skin. Humans acquire the infection from contact with infected animals, carcasses, or contaminated, nonliving material. […] Autoinoculation to the genital area and face can occur, but human-to-human transmission is rare and there are reports in the literature of six possible cases. […] The orf virus is a cylindrical virus measuring 260 X 160 nm. Its surface tubules form a long crisscross design that is seen on negatively stained preparations by electron microscopy. […] The B2L major envelope protein has lipase activity and immunomodulating properties.
  • #3 Contagious Ecthyma in Sheep and Goats – Integumentary System – Merck Veterinary Manual
    https://www.merckvetmanual.com/integumentary-system/pox-diseases/contagious-ecthyma-in-sheep-and-goats
    Contagious ecthyma is a viral, pustular dermatitis of young sheep and goats. […] The parapoxvirus that causes contagious ecthyma is related to the viruses that cause pseudocowpox and bovine papular stomatitis. […] The primary lesion of contagious ecthyma develops at the mucocutaneous junction of the lips and around erupting incisor teeth, and it may extend to the mucosa of the buccal cavity. […] The ecthyma lesion is characteristic. […] The virus is transmissible to humans; lesions in humans are usually confined to the hands and face, are more proliferative, and can be very distressing. […] Sheep that have recovered from natural infection are highly resistant to reinfection. […] Live vaccines should be administered cautiously to avoid contaminating uninfected premises, and vaccinated animals should be segregated from unprotected stock until the scabs have fallen off.
  • #4 Orf: Practice Essentials, Pathophysiology, Epidemiology
    https://emedicine.medscape.com/article/1133450-overview
    Orf is caused by infection with the orf virus that belongs to the Parapoxvirus genus, which also includes the milker’s nodule virus. […] The orf virus is able to produce a homolog of anti-inflammatory cytokine, interleukin (IL)10, which contributes to localized suppression of immunity. […] Orf is transmitted by direct contact inoculation usually via a wound in the skin. Humans acquire the infection from contact with infected animals, carcasses, or contaminated, nonliving material. […] Autoinoculation to the genital area and face can occur, but human-to-human transmission is rare and there are reports in the literature of six possible cases. […] The orf virus is a cylindrical virus measuring 260 X 160 nm. Its surface tubules form a long crisscross design that is seen on negatively stained preparations by electron microscopy. […] The B2L major envelope protein has lipase activity and immunomodulating properties.
  • #5 Contagious Ecthyma in Sheep and Goats – Integumentary System – Merck Veterinary Manual
    https://www.merckvetmanual.com/integumentary-system/pox-diseases/contagious-ecthyma-in-sheep-and-goats
    Orf virus (ORFV) is the prototype of the genus Parapoxvirus (PPV). […] The ORFV genome has 132 genes. […] The origin of ORFV is not known; however, the relationship among different PPVs on the orf011 gene suggests that it could be closely related to PCPV. […] Phylogenetic analysis based on the orf011 gene (B2L protein) indicates that PCPV and ORFV are closely related.
  • #6 Studies of the pathogenesis of orf virus infection in sheep – PubMed
    https://pubmed.ncbi.nlm.nih.gov/3204166/
    Damage to the skin is essential for the establishment of orf virus infection and the development of typical lesions. […] However, analysis of the pathogenesis of experimental lesions induced by viral challenge of mildly abraded skin, indicated that the virus does not establish in the damaged epidermis, but replicates in the cells of an underlying replacement epidermal layer derived from the walls of the wool follicles. […] The skin reaction consists of a cellular response with necrosis and sloughing of the affected epidermis and underlying stratum papillare of the dermis. […] Healing is then completed by the formation of a third epidermis derived from the deeper portions of the wool follicles.
  • #7 Studies of the pathogenesis of orf virus infection in sheep – PubMed
    https://pubmed.ncbi.nlm.nih.gov/3204166/
    Damage to the skin is essential for the establishment of orf virus infection and the development of typical lesions. […] However, analysis of the pathogenesis of experimental lesions induced by viral challenge of mildly abraded skin, indicated that the virus does not establish in the damaged epidermis, but replicates in the cells of an underlying replacement epidermal layer derived from the walls of the wool follicles. […] The skin reaction consists of a cellular response with necrosis and sloughing of the affected epidermis and underlying stratum papillare of the dermis. […] Healing is then completed by the formation of a third epidermis derived from the deeper portions of the wool follicles.
  • #8 Contagious Ecthyma in Sheep and Goats – Integumentary System – Merck Veterinary Manual
    https://www.merckvetmanual.com/integumentary-system/pox-diseases/contagious-ecthyma-in-sheep-and-goats
    Contagious ecthyma is a viral, pustular dermatitis of young sheep and goats. […] The parapoxvirus that causes contagious ecthyma is related to the viruses that cause pseudocowpox and bovine papular stomatitis. […] The primary lesion of contagious ecthyma develops at the mucocutaneous junction of the lips and around erupting incisor teeth, and it may extend to the mucosa of the buccal cavity. […] The ecthyma lesion is characteristic. […] The virus is transmissible to humans; lesions in humans are usually confined to the hands and face, are more proliferative, and can be very distressing. […] Sheep that have recovered from natural infection are highly resistant to reinfection. […] Live vaccines should be administered cautiously to avoid contaminating uninfected premises, and vaccinated animals should be segregated from unprotected stock until the scabs have fallen off.
  • #9 Orf Viral Infection – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK562191/
    Orf viral infection, also known as ecthyma contagiosum or contagious pustular dermatitis, is an occupational disease primarily acquired from infected sheep and goats. […] Orf is caused by the parapoxvirus Orfviridae. The orf virus plagues young sheep and goats, which are their natural host range. […] The orf virus uses various immunomodulatory effects to evade the immune system and infect keratinocytes. […] Further research findings have demonstrated that the orf virus uses macroautophagy in mammals, possibly contributing to the viral infection and pathogenesis in human hosts. […] The orf virus demonstrates immunomodulatory and antiviral activity, including antifibrotic activity, as observed in hepatic samples from rats infected with hepatitis B virus and hepatitis C virus. […] The infection caused by the orf virus is endemic to sheep and goats. Direct contact with active lesions from affected animals or contact with fomites can infect humans. […] Orf virus is rarely, if ever, transmitted from humans to other humans.
  • #10 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    Orf is one of the most widespread viral diseases worldwide, usually benign and self-limiting, and mainly affects not only sheep and goats, but also various other ruminants and mammals. […] ORFV encodes virulence and immunomodulatory factors that interfere with host inflammatory effect and antiviral immune mechanisms and induces a transient and complex cytokine response, initially represented by Th1-related cytokines followed by Th2-related cytokines. […] The ORFV has evolved several mechanisms to survive in the presence of the immune system, resulting in repeated infections. […] ORFV is widely recognized as having a powerful host immunoregulatory function. […] ORFV can quickly mediate humoral and adaptive immune responses. […] ORFV and some of its encoded proteins have a good immunomodulatory function.
  • #11 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    Orf, also called contagious ecthyma or contagious pustular dermatitis, is a zoonotic viral skin disease caused by orf virus (ORFV). ORFV develops various virulence factors that work alone or coordinate with each other assisting the virus in immune evasion and host infection. […] Major virulence genes in ITRs included ORFV homologous ovine gene encoding cytokine IL-10 (vIL-10), ORFV interferon resistance gene (OVIFNR), vascular endothelial growth factor (VEGF) the virus encoding chemokine binding protein (vCBP), ankyrin (ANK), dUTP pyrophosphatase (dUTPase), granulocyte-macrophage colony stimulating factor (GM-CSF) inhibiting factor (GIF), apoptosis inducing and inhibiting genes and ORFV121 gene that inhibits the host NF-B pathway. […] During the evolution and interaction with the hosts, ORFV develops a set of immune regulation strategy for replication and immune evasion, by taking advantage of various virulence factors.
  • #12 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    ORFV uses ORFV121 in order to disturb the host transcription and impair host immune response through inhibiting the NF-B pathway signal transduction, such that it can successfully evade the host immune system. […] ORFV expresses the 5 ANK proteins that degrade the host’s anti-virus factors through the F-box-like domains, thereby promoting the ORFV replication and infection of different species. […] vIL-10 inhibits the maturation and function of antigen presenting cells (APCs) such as dendrite cells (DCs), which could inhibit the proliferation and transcription of a range of Th1 cell cytokines including IL-2, IL-3, IFN- and GM-CSF. […] vIL-10 inhibits the immune responses and provides suitable environment for the ORFV infection. […] VEGFs enhance the proliferation of endothelial cells and increase the vascular permeability which is facilitated by the viral replication and pustule formation.
  • #13 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    The ORFV develops a protein against the host IFN response that is encoded by the ORFV interferon resistance gene (OVIFNR). This protein binds to the viral double-stranded (ds) DNA, inhibits the dsDNA-dependent activation of IFN-inducible protein kinase (PKR) and prevents the down-regulation of viral mRNA transcription. […] ORFV can synthesize vCBP, a 2.5 protein with hexagonal crystal structure, that binds the receptors as competitive inhibitors of homogenous cytokines and inhibits inflammation by preventing monocytes and DCs from transferring into the skin inflammatory lesions or peripheral lymph nodes. […] The GIF can specifically inhibit the biological activity of IL-2 and GM-CSF. […] The ORFV121 encodes a novel NF-B inhibitor that binds to NF-B and inhibits the phosphorylation and nuclear translocation of NF-kB-p65 thereby inhibiting the translation of the immune-related genes.
  • #14 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    ORFV uses ORFV121 in order to disturb the host transcription and impair host immune response through inhibiting the NF-B pathway signal transduction, such that it can successfully evade the host immune system. […] ORFV expresses the 5 ANK proteins that degrade the host’s anti-virus factors through the F-box-like domains, thereby promoting the ORFV replication and infection of different species. […] vIL-10 inhibits the maturation and function of antigen presenting cells (APCs) such as dendrite cells (DCs), which could inhibit the proliferation and transcription of a range of Th1 cell cytokines including IL-2, IL-3, IFN- and GM-CSF. […] vIL-10 inhibits the immune responses and provides suitable environment for the ORFV infection. […] VEGFs enhance the proliferation of endothelial cells and increase the vascular permeability which is facilitated by the viral replication and pustule formation.
  • #15 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    The ORFV develops a protein against the host IFN response that is encoded by the ORFV interferon resistance gene (OVIFNR). This protein binds to the viral double-stranded (ds) DNA, inhibits the dsDNA-dependent activation of IFN-inducible protein kinase (PKR) and prevents the down-regulation of viral mRNA transcription. […] ORFV can synthesize vCBP, a 2.5 protein with hexagonal crystal structure, that binds the receptors as competitive inhibitors of homogenous cytokines and inhibits inflammation by preventing monocytes and DCs from transferring into the skin inflammatory lesions or peripheral lymph nodes. […] The GIF can specifically inhibit the biological activity of IL-2 and GM-CSF. […] The ORFV121 encodes a novel NF-B inhibitor that binds to NF-B and inhibits the phosphorylation and nuclear translocation of NF-kB-p65 thereby inhibiting the translation of the immune-related genes.
  • #16 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    ORFV uses ORFV121 in order to disturb the host transcription and impair host immune response through inhibiting the NF-B pathway signal transduction, such that it can successfully evade the host immune system. […] ORFV expresses the 5 ANK proteins that degrade the host’s anti-virus factors through the F-box-like domains, thereby promoting the ORFV replication and infection of different species. […] vIL-10 inhibits the maturation and function of antigen presenting cells (APCs) such as dendrite cells (DCs), which could inhibit the proliferation and transcription of a range of Th1 cell cytokines including IL-2, IL-3, IFN- and GM-CSF. […] vIL-10 inhibits the immune responses and provides suitable environment for the ORFV infection. […] VEGFs enhance the proliferation of endothelial cells and increase the vascular permeability which is facilitated by the viral replication and pustule formation.
  • #17 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    The main targets of IFN resistance genes are host cytokines, chemokines, NF-B signaling pathway, and apoptosis pathway. […] The ORFV007-encoded dUTPase clusters with mammalian counterparts and is more similar to mammalian dUTPases than to dUTPases from other poxviruses. […] Chemokine-binding protein (CBP), the coding product of ORFV112, has similarities in structure and function with CBP II of orthopoxvirus and rabbit poxvirus. […] ORFV infection stimulated hyperplasia of epidermal cells and capillaries growth with increased vascular permeability, which allows increased virus replication and formation of scabs on wound healing. […] ORFV002-encoded protein can inhibit the activation of NF-B pathway induced by TNF- and ORFV virus infection. […] The ORFV024-encoded protein combines with LAGE3 to inhibit the phosphorylation of IKKs complex and then affects the phosphorylation of NF-B-p65, inhibits the host immune cells to secrete some important cytokines, and regulates the hosts immune response.
  • #18 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    The ORFV develops a protein against the host IFN response that is encoded by the ORFV interferon resistance gene (OVIFNR). This protein binds to the viral double-stranded (ds) DNA, inhibits the dsDNA-dependent activation of IFN-inducible protein kinase (PKR) and prevents the down-regulation of viral mRNA transcription. […] ORFV can synthesize vCBP, a 2.5 protein with hexagonal crystal structure, that binds the receptors as competitive inhibitors of homogenous cytokines and inhibits inflammation by preventing monocytes and DCs from transferring into the skin inflammatory lesions or peripheral lymph nodes. […] The GIF can specifically inhibit the biological activity of IL-2 and GM-CSF. […] The ORFV121 encodes a novel NF-B inhibitor that binds to NF-B and inhibits the phosphorylation and nuclear translocation of NF-kB-p65 thereby inhibiting the translation of the immune-related genes.
  • #19 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    The ORFV develops a protein against the host IFN response that is encoded by the ORFV interferon resistance gene (OVIFNR). This protein binds to the viral double-stranded (ds) DNA, inhibits the dsDNA-dependent activation of IFN-inducible protein kinase (PKR) and prevents the down-regulation of viral mRNA transcription. […] ORFV can synthesize vCBP, a 2.5 protein with hexagonal crystal structure, that binds the receptors as competitive inhibitors of homogenous cytokines and inhibits inflammation by preventing monocytes and DCs from transferring into the skin inflammatory lesions or peripheral lymph nodes. […] The GIF can specifically inhibit the biological activity of IL-2 and GM-CSF. […] The ORFV121 encodes a novel NF-B inhibitor that binds to NF-B and inhibits the phosphorylation and nuclear translocation of NF-kB-p65 thereby inhibiting the translation of the immune-related genes.
  • #20 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    ORFV119 blocks the NF-B signaling largely in a pRb-dependent manner, by inhibiting IKK complex activation early in infection. […] ORFV073 protein is located in nucleus during viral replication and be related to gene expression regulation. […] ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to virus virulence.
  • #21 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    Orf, also called contagious ecthyma or contagious pustular dermatitis, is a zoonotic viral skin disease caused by orf virus (ORFV). ORFV develops various virulence factors that work alone or coordinate with each other assisting the virus in immune evasion and host infection. […] Major virulence genes in ITRs included ORFV homologous ovine gene encoding cytokine IL-10 (vIL-10), ORFV interferon resistance gene (OVIFNR), vascular endothelial growth factor (VEGF) the virus encoding chemokine binding protein (vCBP), ankyrin (ANK), dUTP pyrophosphatase (dUTPase), granulocyte-macrophage colony stimulating factor (GM-CSF) inhibiting factor (GIF), apoptosis inducing and inhibiting genes and ORFV121 gene that inhibits the host NF-B pathway. […] During the evolution and interaction with the hosts, ORFV develops a set of immune regulation strategy for replication and immune evasion, by taking advantage of various virulence factors.
  • #22 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    The main targets of IFN resistance genes are host cytokines, chemokines, NF-B signaling pathway, and apoptosis pathway. […] The ORFV007-encoded dUTPase clusters with mammalian counterparts and is more similar to mammalian dUTPases than to dUTPases from other poxviruses. […] Chemokine-binding protein (CBP), the coding product of ORFV112, has similarities in structure and function with CBP II of orthopoxvirus and rabbit poxvirus. […] ORFV infection stimulated hyperplasia of epidermal cells and capillaries growth with increased vascular permeability, which allows increased virus replication and formation of scabs on wound healing. […] ORFV002-encoded protein can inhibit the activation of NF-B pathway induced by TNF- and ORFV virus infection. […] The ORFV024-encoded protein combines with LAGE3 to inhibit the phosphorylation of IKKs complex and then affects the phosphorylation of NF-B-p65, inhibits the host immune cells to secrete some important cytokines, and regulates the hosts immune response.
  • #23 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    ORFV119 blocks the NF-B signaling largely in a pRb-dependent manner, by inhibiting IKK complex activation early in infection. […] ORFV073 protein is located in nucleus during viral replication and be related to gene expression regulation. […] ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to virus virulence.
  • #24 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    ORFV induced apoptosis in APCs, epidermis cells and lymph cells, mediated through the CD95 pathway. […] Some of the ORFV membrane proteins induce apoptosis in the host APCs and suppress the activation of T cells via CD95/CD95L pathway. […] The novel immune evasion mechanism mediated by this protein encoded by ORFV has not yet been discovered in other viruses. […] ORFV takes advantage of many of the host resources to fight back against the host immune system.
  • #25 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    The ORFV develops a protein against the host IFN response that is encoded by the ORFV interferon resistance gene (OVIFNR). This protein binds to the viral double-stranded (ds) DNA, inhibits the dsDNA-dependent activation of IFN-inducible protein kinase (PKR) and prevents the down-regulation of viral mRNA transcription. […] ORFV can synthesize vCBP, a 2.5 protein with hexagonal crystal structure, that binds the receptors as competitive inhibitors of homogenous cytokines and inhibits inflammation by preventing monocytes and DCs from transferring into the skin inflammatory lesions or peripheral lymph nodes. […] The GIF can specifically inhibit the biological activity of IL-2 and GM-CSF. […] The ORFV121 encodes a novel NF-B inhibitor that binds to NF-B and inhibits the phosphorylation and nuclear translocation of NF-kB-p65 thereby inhibiting the translation of the immune-related genes.
  • #26 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    The main targets of IFN resistance genes are host cytokines, chemokines, NF-B signaling pathway, and apoptosis pathway. […] The ORFV007-encoded dUTPase clusters with mammalian counterparts and is more similar to mammalian dUTPases than to dUTPases from other poxviruses. […] Chemokine-binding protein (CBP), the coding product of ORFV112, has similarities in structure and function with CBP II of orthopoxvirus and rabbit poxvirus. […] ORFV infection stimulated hyperplasia of epidermal cells and capillaries growth with increased vascular permeability, which allows increased virus replication and formation of scabs on wound healing. […] ORFV002-encoded protein can inhibit the activation of NF-B pathway induced by TNF- and ORFV virus infection. […] The ORFV024-encoded protein combines with LAGE3 to inhibit the phosphorylation of IKKs complex and then affects the phosphorylation of NF-B-p65, inhibits the host immune cells to secrete some important cytokines, and regulates the hosts immune response.
  • #27 Contagious Ecthyma in Sheep and Goats – Integumentary System – Merck Veterinary Manual
    https://www.merckvetmanual.com/integumentary-system/pox-diseases/contagious-ecthyma-in-sheep-and-goats
    Contagious ecthyma is a viral, pustular dermatitis of young sheep and goats. […] The parapoxvirus that causes contagious ecthyma is related to the viruses that cause pseudocowpox and bovine papular stomatitis. […] The primary lesion of contagious ecthyma develops at the mucocutaneous junction of the lips and around erupting incisor teeth, and it may extend to the mucosa of the buccal cavity. […] The ecthyma lesion is characteristic. […] The virus is transmissible to humans; lesions in humans are usually confined to the hands and face, are more proliferative, and can be very distressing. […] Sheep that have recovered from natural infection are highly resistant to reinfection. […] Live vaccines should be administered cautiously to avoid contaminating uninfected premises, and vaccinated animals should be segregated from unprotected stock until the scabs have fallen off.
  • #28 Contagious Ecthyma in Sheep and Goats – Integumentary System – Merck Veterinary Manual
    https://www.merckvetmanual.com/integumentary-system/pox-diseases/contagious-ecthyma-in-sheep-and-goats
    Contagious ecthyma is a viral, pustular dermatitis of young sheep and goats. […] The parapoxvirus that causes contagious ecthyma is related to the viruses that cause pseudocowpox and bovine papular stomatitis. […] The primary lesion of contagious ecthyma develops at the mucocutaneous junction of the lips and around erupting incisor teeth, and it may extend to the mucosa of the buccal cavity. […] The ecthyma lesion is characteristic. […] The virus is transmissible to humans; lesions in humans are usually confined to the hands and face, are more proliferative, and can be very distressing. […] Sheep that have recovered from natural infection are highly resistant to reinfection. […] Live vaccines should be administered cautiously to avoid contaminating uninfected premises, and vaccinated animals should be segregated from unprotected stock until the scabs have fallen off.
  • #29 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    Orf is one of the most widespread viral diseases worldwide, usually benign and self-limiting, and mainly affects not only sheep and goats, but also various other ruminants and mammals. […] ORFV encodes virulence and immunomodulatory factors that interfere with host inflammatory effect and antiviral immune mechanisms and induces a transient and complex cytokine response, initially represented by Th1-related cytokines followed by Th2-related cytokines. […] The ORFV has evolved several mechanisms to survive in the presence of the immune system, resulting in repeated infections. […] ORFV is widely recognized as having a powerful host immunoregulatory function. […] ORFV can quickly mediate humoral and adaptive immune responses. […] ORFV and some of its encoded proteins have a good immunomodulatory function.
  • #30 Orf Viral Infection – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK562191/
    Orf viral infection, also known as ecthyma contagiosum or contagious pustular dermatitis, is an occupational disease primarily acquired from infected sheep and goats. […] Orf is caused by the parapoxvirus Orfviridae. The orf virus plagues young sheep and goats, which are their natural host range. […] The orf virus uses various immunomodulatory effects to evade the immune system and infect keratinocytes. […] Further research findings have demonstrated that the orf virus uses macroautophagy in mammals, possibly contributing to the viral infection and pathogenesis in human hosts. […] The orf virus demonstrates immunomodulatory and antiviral activity, including antifibrotic activity, as observed in hepatic samples from rats infected with hepatitis B virus and hepatitis C virus. […] The infection caused by the orf virus is endemic to sheep and goats. Direct contact with active lesions from affected animals or contact with fomites can infect humans. […] Orf virus is rarely, if ever, transmitted from humans to other humans.
  • #31 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    Orf is one of the most widespread viral diseases worldwide, usually benign and self-limiting, and mainly affects not only sheep and goats, but also various other ruminants and mammals. […] ORFV encodes virulence and immunomodulatory factors that interfere with host inflammatory effect and antiviral immune mechanisms and induces a transient and complex cytokine response, initially represented by Th1-related cytokines followed by Th2-related cytokines. […] The ORFV has evolved several mechanisms to survive in the presence of the immune system, resulting in repeated infections. […] ORFV is widely recognized as having a powerful host immunoregulatory function. […] ORFV can quickly mediate humoral and adaptive immune responses. […] ORFV and some of its encoded proteins have a good immunomodulatory function.
  • #32 Studies of the pathogenesis of orf virus infection in sheep – PubMed
    https://pubmed.ncbi.nlm.nih.gov/3204166/
    Damage to the skin is essential for the establishment of orf virus infection and the development of typical lesions. […] However, analysis of the pathogenesis of experimental lesions induced by viral challenge of mildly abraded skin, indicated that the virus does not establish in the damaged epidermis, but replicates in the cells of an underlying replacement epidermal layer derived from the walls of the wool follicles. […] The skin reaction consists of a cellular response with necrosis and sloughing of the affected epidermis and underlying stratum papillare of the dermis. […] Healing is then completed by the formation of a third epidermis derived from the deeper portions of the wool follicles.
  • #33 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    Orf, also called contagious ecthyma or contagious pustular dermatitis, is a zoonotic viral skin disease caused by orf virus (ORFV). ORFV develops various virulence factors that work alone or coordinate with each other assisting the virus in immune evasion and host infection. […] Major virulence genes in ITRs included ORFV homologous ovine gene encoding cytokine IL-10 (vIL-10), ORFV interferon resistance gene (OVIFNR), vascular endothelial growth factor (VEGF) the virus encoding chemokine binding protein (vCBP), ankyrin (ANK), dUTP pyrophosphatase (dUTPase), granulocyte-macrophage colony stimulating factor (GM-CSF) inhibiting factor (GIF), apoptosis inducing and inhibiting genes and ORFV121 gene that inhibits the host NF-B pathway. […] During the evolution and interaction with the hosts, ORFV develops a set of immune regulation strategy for replication and immune evasion, by taking advantage of various virulence factors.
  • #34 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    Orf, also called contagious ecthyma or contagious pustular dermatitis, is a zoonotic viral skin disease caused by orf virus (ORFV). ORFV develops various virulence factors that work alone or coordinate with each other assisting the virus in immune evasion and host infection. […] Major virulence genes in ITRs included ORFV homologous ovine gene encoding cytokine IL-10 (vIL-10), ORFV interferon resistance gene (OVIFNR), vascular endothelial growth factor (VEGF) the virus encoding chemokine binding protein (vCBP), ankyrin (ANK), dUTP pyrophosphatase (dUTPase), granulocyte-macrophage colony stimulating factor (GM-CSF) inhibiting factor (GIF), apoptosis inducing and inhibiting genes and ORFV121 gene that inhibits the host NF-B pathway. […] During the evolution and interaction with the hosts, ORFV develops a set of immune regulation strategy for replication and immune evasion, by taking advantage of various virulence factors.
  • #35 Major Virulence Factors of Orf Virus and Their Mechanism for Immune Evasion
    https://austinpublishinggroup.com/infectious-diseases/fulltext/ajid-v1-id1005.php
    ORFV uses ORFV121 in order to disturb the host transcription and impair host immune response through inhibiting the NF-B pathway signal transduction, such that it can successfully evade the host immune system. […] ORFV expresses the 5 ANK proteins that degrade the host’s anti-virus factors through the F-box-like domains, thereby promoting the ORFV replication and infection of different species. […] vIL-10 inhibits the maturation and function of antigen presenting cells (APCs) such as dendrite cells (DCs), which could inhibit the proliferation and transcription of a range of Th1 cell cytokines including IL-2, IL-3, IFN- and GM-CSF. […] vIL-10 inhibits the immune responses and provides suitable environment for the ORFV infection. […] VEGFs enhance the proliferation of endothelial cells and increase the vascular permeability which is facilitated by the viral replication and pustule formation.
  • #36 Orf Virus: A New Class of Immunotherapy Drugs | IntechOpen
    https://www.intechopen.com/chapters/64011
    The main targets of IFN resistance genes are host cytokines, chemokines, NF-B signaling pathway, and apoptosis pathway. […] The ORFV007-encoded dUTPase clusters with mammalian counterparts and is more similar to mammalian dUTPases than to dUTPases from other poxviruses. […] Chemokine-binding protein (CBP), the coding product of ORFV112, has similarities in structure and function with CBP II of orthopoxvirus and rabbit poxvirus. […] ORFV infection stimulated hyperplasia of epidermal cells and capillaries growth with increased vascular permeability, which allows increased virus replication and formation of scabs on wound healing. […] ORFV002-encoded protein can inhibit the activation of NF-B pathway induced by TNF- and ORFV virus infection. […] The ORFV024-encoded protein combines with LAGE3 to inhibit the phosphorylation of IKKs complex and then affects the phosphorylation of NF-B-p65, inhibits the host immune cells to secrete some important cytokines, and regulates the hosts immune response.

Zobacz więcej

czynnik zjadliwości wirus orf parapoxvirus przepuszczalność naczyń modulacja odpowiedzi immunologicznej odpowiedź cytokinowa czynnik wzrostu śródbłonka naczyniowego dermatitis pęcherzycowa ecthyma contagiosum wirus zapalenia wątroby typu B komórka prezentująca antygen choroba wirusowa skóry pęcherzyca zakaźna działanie przeciwzwłóknieniowe makroautofagia białko wirulencji wirus zapalenia wątroby typu C komórka dendrytyczna odpowiedź humoralna choroba odzwierzęca indukcja apoptozy