The Journal of Experimental Medicine
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Published online 2 April 2001.
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© The Rockefeller University Press, 0022-1007/2001/4/847/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 7, April 2, 2001 847-854

Original Article

Kinetics of Acute Hepatitis B Virus Infection in Humans

Simon A. Whalleya, John M. Murrayc,d, Dave Browna, George J.M. Webstera, Vincent C. Emeryb, Geoffrey M. Dusheikoa, and Alan S. Perelsonc
a Centre for Hepatology, Department of Medicine, Royal Free Campus,
b Department of Virology, Royal Free and University College Medical School, London NW3 2QG, United Kingdom
c Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545
d School of Mathematics, University of New South Wales, Sydney NSW 2052, Australia

Correspondence to: Alan S. Perelson, Theoretical Div., MS-K710, Los Alamos National Laboratory, Los Alamos, NM 87545. Tel:505-667-6829 Fax:505-665-3493 E-mail:asp{at}lanl.gov.

Using patient data from a unique single source outbreak of hepatitis B virus (HBV) infection, we have characterized the kinetics of acute HBV infection by monitoring viral turnover in the serum during the late incubation and clinical phases of the disease in humans. HBV replicates rapidly with minimally estimated doubling times ranging between 2.2 and 5.8 d (mean 3.7 ± 1.5 d). After a peak viral load in serum of nearly 1010 HBV DNA copies/ml is attained, clearance of HBV DNA follows a two or three phase decay pattern with an initial rapid decline characterized by mean half-life (t1/2) of 3.7 ± 1.2 d, similar to the t1/2 observed in the noncytolytic clearance of covalently closed circular DNA for other hepadnaviruses. The final phase of virion clearance occurs at a variable rate (t1/2 of 4.8 to 284 d) and may relate to the rate of loss of infected hepatocytes. Free virus has a mean t1/2 of at most 1.2 ± 0.6 d. We estimate a peak HBV production rate of at least 1013 virions/day and a maximum production rate of an infected hepatocyte of 200–1,000 virions/day, on average. At this peak rate of virion production we estimate that every possible single and most double mutations would be created each day.

Key Words: acute hepatitis B, kinetics, cytotoxic T lymphocytes, mutation, hepatocyte


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