Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9245504 | Gastroenterology | 2005 | 11 Pages |
Abstract
Background & Aims: Although hepatitis C virus kinetics and immune determinants during primary infection have been described, the virus-host interplay is not fully understood. We used mathematical modeling to elucidate and quantify virus-host dynamics. Methods: Ten chimpanzees were infected intrahepatically with H77-RNA (n = 3) or intravenously with infected serum. Blood samples were taken 1-3 times per week for 6 months. A new model was fitted to the observed HCV RNA and alanine aminotransferase (ALT) kinetics. Results: After infection, viral levels increased in a biphasic manner with a transient decline in between. This can be explained by a partial block (mean, 91%) of virion production, possibly due to an endogenous type I interferon response. After reaching maximum levels, a long viral plateau (mean, 6.1 log cp/mL) can be explained by blind homeostasis and lack of susceptible cells. Modest elevations in ALT levels (21-93 IU/L) were concurrently observed, indicating a shorter half-life of infected versus noninfected hepatocytes (mean ratio, 2.6). Following the ALT flare, viral titers rapidly declined to a lower (mean, 4.5 log cp/mL; n = 6) or undetectable level (n = 4). This decline is compatible with increased cell death (mean minimal estimate half-life, 28.7 days) and noncytolytic clearance (mean maximal estimate half-life, 24.1 days) of infected cells. Conclusions: Our results quantify virus-host dynamics during primary HCV infection and suggest that endogenous type I interferon slows virus production in the early acute phase. Partial or effective virus control correlates with the half-life of infected cells regulated by both cytolytic and noncytolytic mechanisms.
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Authors
Harel Dahari, Marian Major, Xinan Zhang, Kathleen Mihalik, Charles M. Rice, Alan S. Perelson, Stephen M. Feinstone, Avidan U. Neumann,