eprintid: 10187003 rev_number: 6 eprint_status: archive userid: 699 dir: disk0/10/18/70/03 datestamp: 2024-02-12 16:34:04 lastmod: 2024-02-12 16:34:04 status_changed: 2024-02-12 16:34:04 type: article metadata_visibility: show sword_depositor: 699 creators_name: Chen, Qin-Yan creators_name: Jia, Hui-Hua creators_name: Wang, Xue-Yan creators_name: Shi, Yun-Liang creators_name: Zhang, Lu-Juan creators_name: Hu, Li-Ping creators_name: Wang, Chao creators_name: He, Xiang creators_name: Harrison, Tim J creators_name: Jackson, J Brooks creators_name: Wu, Li creators_name: Fang, Zhong-Liao title: Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 keywords: Hepatitis B virus, Evolution, Mutation, Reversion, Next-generation sequencing note: © 2021 The Authors. Published by Elsevier B.V. under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 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. date: 2022-01-24 date_type: published publisher: ELSEVIER official_url: http://dx.doi.org/10.1016/j.meegid.2021.105184 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1913622 doi: 10.1016/j.meegid.2021.105184 medium: Print-Electronic pii: S1567-1348(21)00484-6 lyricists_name: Harrison, Tim lyricists_id: THARR65 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner funding_acknowledgements: [Global Health Research Seed Grant from the Carver College of Medicine at the University of Iowa]; 81860595 [National Natural Science Foundation of China]; 81703283 [National Natural Science Foundation of China]; 2018AB59002 [Guangxi Key Research and Development Project]; 2017GXNSFBA198086 [Guangxi Natural Science Foundation] full_text_status: public publication: Infection, Genetics and Evolution volume: 97 article_number: 105184 pages: 12 event_location: Netherlands citation: 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 <#> Chen, Qin-Yan; Jia, Hui-Hua; Wang, Xue-Yan; Shi, Yun-Liang; Zhang, Lu-Juan; Hu, Li-Ping; Wang, Chao; He, Xiang; Harrison, Tim J; Jackson, J Brooks; Wu, Li; Fang, Zhong-Liao; - view fewer <#> (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 <https://doi.org/10.1016/j.meegid.2021.105184>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10187003/1/1-s2.0-S1567134821004846-main.pdf