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Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study

Chen, Qin-Yan; Jia, Hui-Hua; Wang, Xue-Yan; Shi, Yun-Liang; Zhang, Lu-Juan; Hu, Li-Ping; Wang, Chao; ... Fang, Zhong-Liao; + view all (2022) Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study. Infection, Genetics and Evolution , 97 , Article 105184. 10.1016/j.meegid.2021.105184. Green open access

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Abstract

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.

Type: Article
Title: Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.meegid.2021.105184
Publisher version: http://dx.doi.org/10.1016/j.meegid.2021.105184
Language: English
Additional information: © 2021 The Authors. Published by Elsevier B.V. under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Hepatitis B virus, Evolution, Mutation, Reversion, Next-generation sequencing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10187003
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