Analysis of hepatitis C virus-inoculated chimpanzees reveals unexpected clinical profiles.
The clinical course of hepatitis C virus (HCV) infections in a chimpanzee cohort was examined to better characterize the outcome of this valuable animal model. Results of a cross-sectional study revealed that a low percentage (39%) of HCV-inoculated chimpanzees were viremic based on reverse transcription (RT-PCR) analysis. A correlation was observed between viremia and the presence of anti-HCV antibodies. The pattern of antibodies was dissimilar among viremic chimpanzees and chimpanzees that cleared the virus. Viremic chimpanzees had a higher prevalence of antibody reactivity to NS3, NS4, and NS5. Since an unexpectedly low percentage of chimpanzees were persistently infected with HCV, a longitudinal analysis of the virological profile of a small panel of HCV-infected chimpanzees was performed to determine the kinetics of viral clearance and loss of antibody. This study also revealed that a low percentage (33%) of HCV-inoculated chimpanzees were persistently viremic. Analysis of serial bleeds from six HCV-infected animals revealed four different clinical profiles. Viral clearance with either gradual or rapid loss of anti-HCV antibody was observed in four animals within 5 months postinoculation. A chronic-carrier profile characterized by persistent HCV RNA and anti-HCV antibody was observed in two animals. One of these chimpanzees was RT-PCR positive, antibody negative for 5 years and thus represented a silent carrier. If extrapolated to the human population, these data would imply that a significant percentage of unrecognized HCV infections may occur and that silent carriers may represent potentially infectious blood donors.
Bassett
S E
SE
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227, USA.
Brasky
K M
KM
Lanford
R E
RE
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002213:Capsid / Q000276:immunology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003546:Cysteine Endopeptidases / Q000276:immunology; D004195:Disease Models, Animal; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology* / Q000503:physiopathology / Q000821:virology*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D002679:Pan troglodytes; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins / Q000276:immunology; D017735:Virus Latency; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000410:Alanine Transaminase; D003546:Cysteine Endopeptidases; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C107824:NS2-3 protease