Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study
Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study
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一项为期 15 年的跟踪研究，对整个乙型肝炎病毒基因组的分析揭示了自然感染中突变向野生型的逆转
DOI：
10.1016/j.meegid.2021.105184
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发表时间：
2021-12-24
影响因子：
3.2
通讯作者：
Fang, Zhong-Liao
中科院分区：
文献类型：
--
作者：
Chen, Qin-Yan;Jia, Hui-Hua;Fang, Zhong-Liao
有报道称，乙肝病毒基因组中的某些突变可能预测病毒感染的结局。然而，使用下一代测序(NGS)对整个乙肝病毒基因组进行长期纵向分析所得出的进化数据仍然很少。在这项研究中，血清样本来自长期前瞻性队列中无症状的乙肝表面抗原(HBs)携带者。用聚合酶链式反应(PCR)扩增乙肝病毒全基因组，并用NGS测序。对9名受试者的28份时间序列血清样本进行了成功的分析。遗传多样性指数(D)为0.013~0.013，中位数为0.004。宿主内病毒进化速率为2.39E-04~3.11E-03。在2007年来自受试者BO129的所有序列中都发现了nt1762(A-*T)和1764(G-*A)的双重突变和nt1896(G-*A)的停止突变。然而，在2019年，这些位置的大多数序列都是野生型的。在2007年和2013年，研究对象TS115的所有序列中都出现了新台币2920-3040之间的缺失，但在2004年或2019年没有出现这些缺失。研究对象CC246的一些序列曾在2004年、2013年和2019年预测过表面蛋白中的逃逸替换(T123N、G145R)，但2007年的序列都没有这些变化。综上所述，在自然感染中，乙肝病毒的变异可能会回复到野生型。临床医生应该警惕根据突变的存在来预测长期预后。
It has been reported that some mutations in the genome of hepatitis B virus (HBV) may predict the outcome of the virus infection. However, evolutionary data derived from long-term longitudinal analysis of entire HBV genomes using next generation sequencing (NGS) remain rare. In this study, serum samples were collected from asymptomatic hepatitis B surface antigen (HBsAg) carriers from a long-term prospective cohort. The entire HBV genome was amplified by polymerase chain reaction (PCR) and sequenced using NGS. Twenty-eight time series serum samples from nine subjects were successfully analysed. The Shannon entropy (Sn) ranged from 0 to 0.89, with a median value of 0.76, and the genetic diversity (D) ranged from 0 to 0.013, with a median value of 0.004. Intrahost HBV viral evolutionary rates ranged from 2.39E-04 to 3.11E-03. Double mutations at nt1762(A-* T) and 1764(G-* A) and a stop mutation at nt1896(G-* A) were seen in all sequences from subject BO129 in 2007. However, in 2019, most sequences were wild type at these positions. Deletions between nt 2920-3040 were seen in all sequences from subject TS115 in 2007 and 2013 but these were not present in 2004 or 2019. Some sequences from subject CC246 had predicted escape substitutions (T123N, G145R) in the surface protein in 2004, 2013 and 2019 but none of the sequences from 2007 had these changes. In conclusion, HBV mutations may revert to wild type in natural infection. Clinicians should be wary of predicting long-term prognoses on the basis of the presence of mutations.