Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease

丙型肝炎病毒清除、持续和疾病的病毒和免疫决定因素

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作者:Robert Thimme, Jens Bukh, Hans Christian Spangenberg, Stefan Wieland, Janell Pemberton, Carola Steiger, Sugantha Govindarajan, Robert H Purcell, Francis V Chisari

Abstract

To define the early events that determine the outcome of acute hepatitis C virus (HCV) infection, we compared the course of viremia with the peripheral and intrahepatic T cell response and intrahepatic cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers were reached: sustained viral clearance, transient viral clearance followed by chronic infection, and chronic infection that persisted at initial peak titers. The results indicate that HCV spread outpaces the T cell response and that HCV rapidly induces but is not controlled by IFN-alphabeta; that viral clearance follows the entry and accumulation of HCV-specific IFN-gamma-producing T cells in the liver; and that it may not require the destruction of infected cells.

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