Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production.
Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.
Department of Translational Medicine and Department of Hepatology, the First Hospital of Jilin University, Changchun, Jilin, China; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Yang
Y
Wang
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
David R
DR
McGivern
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Liang
L
Cheng
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Guangming
G
Li
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Stanley M
SM
Lemon
Department of Translational Medicine and Department of Hepatology, the First Hospital of Jilin University, Changchun, Jilin, China.
Junqi
J
Niu
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Lishan
L
Su
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Natalia J
NJ
Reszka-Blanco
D002460:Cell Line; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology* / Q000821:virology; D012254:Ribavirin / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D016898:Interferon-alpha; D051193:Toll-Like Receptors; D012254:Ribavirin; D016899:Interferon-beta