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Journal of Virology, January 2003, p. 862-870, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.862-870.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Clearance of Hepatitis C Virus Infection in Chimpanzees May Not Necessarily Correlate with the Appearance of Acquired Immunity

Michael Thomson,1,{dagger} Michelina Nascimbeni,1 Michael B. Havert,1 Marian Major,2 Sophia Gonzales,3 Harvey Alter,4 Stephen M. Feinstone,2 Krishna K. Murthy,3 Barbara Rehermann,1 and T. Jake Liang1*

Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases,1 Department of Transfusion Medicine, Clinical Center, National Institutes of Health,4 Laboratory of Hepatitis Viruses, Division of Viral Products, CBER, Food and Drug Administration, Bethesda, Maryland 20892,2 Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 782273

Received 8 August 2002/ Accepted 1 October 2002

Clearance of hepatitis C virus (HCV) infection in humans and chimpanzees is thought to be associated with the induction of strong T-cell responses. We studied four chimpanzees infected with HCV derived from an infectious full-length HCV genotype 1b cDNA. Two of the chimpanzees cleared the infection to undetectable levels for more than 12 months of follow-up; the other two became persistently infected. Detailed analyses of HCV-specific immune responses were performed during the courses of infection in these chimpanzees. Only weak and transient T helper responses were detected during the acute phase in all four chimpanzees. A comparison of the frequency of gamma interferon (IFN-{gamma})-producing CD4+ and CD8+ T cells in peripheral blood by ELISpot assay did not reveal any correlation between viral clearance and T-cell responses. In addition, analyses of IFN-{gamma}, IFN-{alpha}, and interleukin-4 mRNA levels in liver biopsies, presumably indicative of intrahepatic T-cell responses, revealed no distinct pattern in these chimpanzees with respect to infection outcome. The present study suggests that the outcome of HCV infection in chimpanzees is not necessarily attributable to HCV sequence variation and that chimpanzees may recover from HCV infection by mechanisms other than the induction of readily detectable HCV-specific T-cell responses.

* Corresponding author. Mailing address: Liver Diseases Section, NIDDK, NIH Bldg. 10, Rm. 9B16, 10 Center Dr., Bethesda, MD 20892-1800. Phone: (301) 496-1721. Fax: (301) 402-0491. E-mail: JLiang{at}nih.gov.

{dagger} Present address: Clinical Virology Department, GlaxoSmithKline, Research Triangle Park, NC 27709.

Journal of Virology, January 2003, p. 862-870, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.862-870.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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