Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK.
Viruses. 2011 Feb;3(2):83-101. doi: 10.3390/v3020083.
Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements.
乙型肝炎病毒 (HBV) 基因组是小的、半双链 DNA 环状基因组，包含交替重叠的阅读框，并通过 RNA 中间体阶段进行复制。这种复杂的生物学特性给估计 HBV 的进化率带来了挑战，导致难以解析病毒的进化和流行病学历史。在这里，我们使用来自南太平洋土著人群的 112 个个体内传播史（系谱）和个体间基因组的新数据集，结合 313 个先前发表的 HBV 基因组，重新研究了 HBV 的进化率。我们采用贝叶斯系统发育方法来研究 HBV 进化率变化的几个潜在原因和后果。我们的结果揭示了基因型之间和整个基因组范围内的速率变化，以及与乙型肝炎 e 抗原阴性状态相比，在乙型肝炎 e 抗原阳性状态下采样时的速率明显较慢。这种乙型肝炎 e 抗原的速率变化主要归因于感染过程中前核心和核心基因及其调控元件的变化。
