Whalley S A, Murray J M, Brown D, Webster G J, Emery V C, Dusheiko G M, Perelson A S
Centre for Hepatology, Department of Medicine, Royal Free Campus, United Kingdom.
J Exp Med. 2001 Apr 2;193(7):847-54. doi: 10.1084/jem.193.7.847.
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 10(10) 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 (t(1/2)) of 3.7 +/- 1.2 d, similar to the t(1/2) observed in the noncytolytic clearance of covalently closed circular DNA for other hepadnaviruses. The final phase of virion clearance occurs at a variable rate (t(1/2) of 4.8 to 284 d) and 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 rate of at least 10(13) 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.
利用来自单一来源的独特乙肝病毒（HBV）感染暴发的患者数据，我们通过监测人类疾病潜伏期后期和临床阶段血清中的病毒周转情况，对急性HBV感染的动力学特征进行了描述。HBV复制迅速，估计最短倍增时间在2.2至5.8天之间（平均3.7±1.5天）。血清中病毒载量达到近10¹⁰ HBV DNA拷贝/ml的峰值后，HBV DNA的清除遵循两阶段或三阶段衰减模式，初始快速下降阶段的平均半衰期（t₁/₂）为3.7±1.2天，这与其他嗜肝DNA病毒共价闭合环状DNA的非细胞溶解性清除中观察到的t₁/₂相似。病毒颗粒清除的最后阶段以可变速率发生（t₁/₂为4.8至284天），可能与受感染肝细胞的损失速率有关。游离病毒的平均t₁/₂最多为1.2±0.6天。我们估计HBV的峰值产生率至少为每天10¹³个病毒颗粒，受感染肝细胞的最大产生率平均为每天200 - 1000个病毒颗粒。在这个病毒颗粒产生的峰值速率下，我们估计每天会产生每一种可能的单突变和大多数双突变。
