Tedder Richard S, Bissett Sara L, Myers Richard, Ijaz Samreen
Division of Infection and Immunity, UCL, London, UK.
Antivir Ther. 2013;18(3 Pt B):489-96. doi: 10.3851/IMP2655. Epub 2013 Jun 21.
Estimates for the evolutionary rate of HBV until now have been interpreted as showing that HBV is a relatively recent acquisition for mankind. The existence of defined HBV genotypes is thought to represent past founder effects. We have explored virus mutation in a group of 48 persistently infected blood donors sampled at two points in time and suggest otherwise.
HBV-infected donors were detected by hepatitis B surface antigen (HBsAg) screening and staged by hepatitis B e markers. Serum DNA from those persistently infected with HBV was characterized by consensus sequencing and the amino acid sequences inferred. These were compared against consensus genotype sequences and divergence measured at two points in time.
Rates of viral mutation were higher across both HBsAg and hepatitis B core antigen in the group of donors seropositive for hepatitis B e antibody (1.36×10⁻³ and 1.54×10⁻³ changes per residue per year, respectively) than in those seropositive for hepatitis B e antigen (4.59×10⁻⁴ and 6.62×10⁻⁴ changes per residue per year, respectively). Codon mutations reverting to the genotype consensus were commonly seen. Codon changes were clustered close to the C-terminal region of HBsAg and were accommodated in overlapping polymerase by synonymous substitutions.
It is suggested that in vivo HBV behaves as a self-normalizing meme and mutational rates, although high, do not lead to significant change over time in a persistent infection. This would be compatible with co-evolution within its human host and introduction within humans being an ancient occurrence.
迄今为止，对乙肝病毒（HBV）进化速率的估计被解释为表明HBV是人类相对较新获得的病毒。已确定的HBV基因型的存在被认为代表了过去的奠基者效应。我们对一组48名在两个时间点采样的持续感染献血者的病毒突变进行了研究，结果却并非如此。
通过乙肝表面抗原（HBsAg）筛查检测HBV感染的献血者，并根据乙肝e抗原标志物进行分期。对那些持续感染HBV者的血清DNA进行一致性测序并推断氨基酸序列。将这些序列与一致性基因型序列进行比较，并测量两个时间点的差异。
乙肝e抗体血清阳性的献血者组中，HBsAg和乙肝核心抗原的病毒突变率（分别为每年每个残基1.36×10⁻³和1.54×10⁻³变化）高于乙肝e抗原血清阳性者（分别为每年每个残基4.59×10⁻⁴和6.62×10⁻⁴变化）。常见到密码子突变恢复为基因型一致性。密码子变化集中在HBsAg的C末端区域附近，并通过同义替换容纳在重叠的聚合酶中。
提示体内HBV表现为一种自我归一化的模因，尽管突变率很高，但在持续感染中随着时间推移不会导致显著变化。这与它在人类宿主内的共同进化以及在人类中的引入是一个古老事件相一致。
