IFN-alpha/RBV resistance mechanisms in persistently infected HCV cell culture

Combination therapy utilizing interferon- alpha (IFN- alpha ), ribavirin (RBV), and a protease or polymerase inhibitor is the current standard of care for HCV genotype 1 infection. Although, this triple combination therapy has significantly improved the sustained virological response (SVR) of chroni...

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Bibliographic Details
Published in:Antiviral therapy 2014-01, Vol.19, p.A44-A44
Main Authors: Dash, S, Chandra, P K, Shores, N, Wu, T, Balart, L A
Format: Article
Language:English
Subjects:
Hepatitis C virus
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Summary:Combination therapy utilizing interferon- alpha (IFN- alpha ), ribavirin (RBV), and a protease or polymerase inhibitor is the current standard of care for HCV genotype 1 infection. Although, this triple combination therapy has significantly improved the sustained virological response (SVR) of chronic HCV 1a infection, the treatment response has not improved significantly among prior non-responders to peginterferon and ribavirin. Therefore a better understanding of the HCV clearance mechanisms by IFN- alpha and RBV may lead to improvements in treatment. A stable and persistent HCV replication cell culture model was developed in Huh 7.5 cells to examine the clearance of viral replication during long-term treatment using IFN- alpha , interferon-[lambda] (IFN [lambda]), and RBV. The results suggest that HCV induced ER-stress and the autophagy response selectively impair type I, but not type III IFN signaling, which is why IFN-[lambda] showed a sustained antiviral response against HCV. Inhibiting ER stress and the autophagy response overcomes IFN- alpha plus RBV resistance mechanisms associated with HCV infection.
ISSN:1359-6535