Kinetics of acute hepatitis B virus infection in humans

Using patient data from a unique single source outbreak of hepatitis B viru s (HBV) infection, we have characterized the kinetics of acute HBV infectio n by monitoring viral turnover in the serum during the late incubation and clinical phases of the disease in humans. HBV replicates rapidly with minim ally 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 10(10) HBV DNA copies/ml is attained, clearance of HBV DNA follows a two or three phase decay patter n with an initial rapid decline characterized by mean half-life (t(1/2)) of 3.7 +/- 1.2 d, similar to the t(1/2) observed in the noncytolytic clearanc e of covalently closed circular DNA for other hepadnaviruses. The final pha se of virion clearance occurs at a variable rate (t(1/2) of 4.8 to 284 d) a nd may relate to the rate of loss of infected hepatocytes. Free virus has a mean t(1/2) of at most 1.2 +/- 0.6 d. We estimate a peak HBV production ra te of at least 10(13) virions/day and a maximum production rate of an infec ted hepatocyte of 200-1,000 virions/day, on average. At this peak rate of v irion production we estimate that every possible single and most double mut ations would be created each day.