Longitudinal Analysis of Hepatitis C Virus Infection and Genetic Drift of the Hypervariable Region

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Abstract
Hepatitis C virus (HCV) infections in a cohort of chimpanzees were studied retrospectively. All animals had been inoculated intravenously with materials derived from a single-source chimpanzee plasma implicated in non-A, non-B hepatitis, prepared by extensive ultracentrifugation. Anti-HCV and HCV RNA were monitored by the confirmatory line immunoassay and by an RNA-capture polymerase chain reaction method, respectively. In a chronically infected chimpanzee, HCV RNA was detectable after 32 days and throughout the acute phase, dropped transiently below detection level, and became detectable again. In 3 other chimpanzees with acute resolving infections, HCV RNA was detected 7–11 days after inoculation and became permanently undetectable after alanine aminotransferase normalization. Various anti-HCV profiles were detected among the chimpanzees. Analysis of the hypervariable region in E2/NS1 in 7 chimpanzees suggested genome stability on transmission, revealed different mutation frequencies during chronic infection, and suggested the importance of immune selection during chronic HCV infection.

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