Article first published online: 1 AUG 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 4, pages 999–1008, October 2007
How to Cite
Lanford, R. E., Guerra, B., Bigger, C. B., Lee, H., Chavez, D. and Brasky, K. M. (2007), Lack of response to exogenous interferon-α in the liver of chimpanzees chronically infected with hepatitis C virus. Hepatology, 46: 999–1008. doi: 10.1002/hep.21776
The full names of the genes indicated by gene symbols in the tables and figures can be found at www.genecards.org.
Potential conflict of interest: Nothing to report.
- Issue published online: 25 SEP 2007
- Article first published online: 1 AUG 2007
- Manuscript Accepted: 14 APR 2007
- Manuscript Received: 20 FEB 2007
- National Institutes of Health. Grant Numbers: R21 DK066755, U19 AI40035, P51 RR13986
The mechanism of the interferon-alpha (IFNα)–induced antiviral response is not completely understood. We recently examined the transcriptional response to IFNα in uninfected chimpanzees. The transcriptional response to IFNα in the liver and peripheral blood mononuclear cells (PBMCs) was rapidly induced but was also rapidly down-regulated, with most interferon-alpha–stimulated genes (ISGs) returning to the baseline within 24 hours. We have extended these observations to include chimpanzees chronically infected with hepatitis C virus (HCV). Remarkably, using total genome microarray analysis, we observed almost no induction of ISG transcripts in the livers of chronically infected animals following IFNα dosing, whereas the response in PBMCs was similar to that in uninfected animals. In agreement with this finding, no decrease in the viral load occurred with up to 12 weeks of pegylated IFNα therapy. The block in the response to exogenous IFNα appeared to be HCV-specific because the response in a hepatitis B virus–infected animal was similar to that of uninfected animals. The lack of a response to exogenous IFNα may be due to an already maximally induced ISG response because chronically HCV-infected chimpanzees already have a highly up-regulated hepatic ISG response. Alternatively, negative regulation may block the response to exogenous IFNα, yet it does not prevent the continued response to endogenous ISG stimuli. The IFNα response in chronically HCV-infected chimpanzees may be mechanistically similar to the null response in the human population. Conclusion: In chimpanzees infected with HCV, the highly elevated hepatic ISG expression may prevent the further induction of ISGs and antiviral efficacy following an IFNα treatment. (HEPATOLOGY 2007.)