Tupaia MAVS Is a Dual Target during Hepatitis C Virus Infection for Innate Immune Evasion and Viral Replication via NF-κB.
J Immunol
; 205(8): 2091-2099, 2020 10 15.
Article
en En
| MEDLINE
| ID: mdl-32907995
ABSTRACT
Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew (Tupaia belangeri chinensis) is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu506 of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-ß but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Tupaia
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Replicación Viral
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FN-kappa B
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Hepatitis C
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Hepacivirus
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Proteínas Adaptadoras Transductoras de Señales
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Evasión Inmune
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Inmunidad Innata
Idioma:
En
Revista:
J Immunol
Año:
2020
Tipo del documento:
Article