Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus.

Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus. Research Abstract Details 

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Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus. Abstract Text:

Robert E Lanford,Bernadette Guerra,Catherine B Bigger,Helen Lee,Deborah Chavez,Kathleen M Brasky,

The mechanism of the interferon-alpha (IFNalpha)-induced antiviral response is not completely understood. We recently examined the transcriptional response to IFNalpha in uninfected chimpanzees. The transcriptional response to IFNalpha 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 IFNalpha 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 IFNalpha therapy. The block in the response to exogenous IFNalpha 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 IFNalpha 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 IFNalpha, yet it does not prevent the continued response to endogenous ISG stimuli. The IFNalpha 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 IFNalpha treatment.

Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus. Publishing Authors By Initials

RE Lanford,B Guerra,CB Bigger,H Lee,D Chavez,KM Brasky,

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Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Hepatology (Baltimore, Md.)

VOLUME: 46

Page Numbers: 999-1008

Journal Abbreviation: Hepatology

ISSN: 0270-9139

DAY: 30

MONTH: Oct

YEAR: 2007

Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus. Information

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LANGUAGE: eng

NlmUniqueID: 8302946

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Grant and Affiliation Information for Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus.

AFFILIATION: Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA. rlanford@icarus.sfbr.org

Country: United States

AGENCY: United States NIAID

GRANT: U19 AI40035

ACRONYM: AI

MEDLINETA: Hepatology

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