Determinants of Viral Clearance and Persistence during Acute Hepatitis C Virus Infection

By R. Thimme, D. Oldach, Kyong‐Mi Chang, Carola Steiger, S. Ray, F. Chisari. Journal of Experimental Medicine, 2001

1,289 citations recorded by the source corpus.

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1–2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-γ− CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38− and started producing IFN-γ in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host–virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.

Subfields: Animal Science and Zoology, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/980e3a3dbc210f6233fc09edea6c881f8f86b5dc

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Citations in the corpus

Memory CD8+ T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection (2003, background): “This clearly differs from the prolonged course of primary infection observed in these animals and reported for other primary infections of humans and chimpanzees (2, 4).”
Immunology of hepatitis B virus and hepatitis C virus infection (2005, background): “In contrast to HBV, HCV reaches high serum titres within 1 week of infectio”
Genetic diversity and evolution of hepatitis C virus--15 years on. (2004, background): “Indeed, recovery from infection is associated with strong and sustained CTL responses around the time of primary infection (Cooper et al., 1999; Lechner et al., 2000; Thimme et al., 2001), a time where there is evidence for specific changes in CTL epitopes and accelerated sequence change in the codi”
The Natural History of Hepatitis C Virus (HCV) Infection (2006, background): “The symptomatic onset ranges from 3 to 12 weeks after exposure.[15, 16] Symptoms may include malaise, weakness, anorexia, and jaundice.”
Immunobiology and pathogenesis of viral hepatitis. (2006, background): “For example, viral persistence has been associated with primary failure to efficiently mount virus-specific CD4 and CD8 T cell responses in both HCV-infected chimpanzees and in a patient who was studied prospectively following accidental needlestick exposure to HCV (8, 78, 130).”