對整個乙型肝炎病毒基因組的分析揭示了自然感染中突變恢

StephenW

對整個乙型肝炎病毒基因組的分析揭示了自然感染中突變恢復為野生型，一項為期 15 年的後續研究
陳欽燕 1 , 賈慧華 2 , 王雪燕 1 , 石雲良 1 , 張璐娟 1 , 胡麗萍 1 , 王超 1 , 賀香 3 , Tim J Harrison 4 , J布魯克斯傑克遜 5 , 李武 6 , 方忠遼 7
隸屬關係
隸屬關係

    1
    廣西壯族自治區疾病預防控制中心, 廣西病毒性肝炎防治重點實驗室, 廣西 南寧 530028.
    2
    廣西壯族自治區疾病預防控制中心, 廣西病毒性肝炎防治重點實驗室, 廣西 南寧 530028;廣西醫科大學臨床前醫學院，廣西南寧雙永路22號 530021
    3
    廣東省疾病預防控制中心廣東省公共衛生研究所，廣東 廣州 511430
    4
    英國倫敦大學學院醫學院醫學系。
    5
    美國愛荷華市愛荷華大學卡佛醫學院病理學系。
    6
    美國愛荷華市愛荷華大學卡佛醫學院微生物學和免疫學系。
    7
    廣西壯族自治區疾病預防控制中心, 廣西病毒性肝炎防治重點實驗室, 廣西 南寧 530028.電子郵箱：[email protected]。

    PMID：34902556 DOI：10.1016/j.meegid.2021.105184

抽象的

據報導，乙型肝炎病毒（HBV）基因組中的一些突變可以預測病毒感染的結果。然而，使用下一代測序 (NGS) 對整個 HBV 基因組進行長期縱向分析的進化數據仍然很少見。在這項研究中，從長期前瞻性隊列中收集了無症狀乙型肝炎表面抗原 (HBsAg) 攜帶者的血清樣本。整個 HBV 基因組通過聚合酶鏈反應 (PCR) 進行擴增，並使用 NGS 進行測序。成功分析了來自 9 個受試者的 28 個時間序列血清樣品。香農熵 (Sn) 的範圍為 0 至 0.89，中值為 0.76，遺傳多樣性 (D) 的範圍為 0 至 0.013，中值為 0.004。宿主內 HBV 病毒進化率範圍從 2.39E-04 到 3.11E-03。在 2007 年受試者 BO129 的所有序列中都發現了 nt1762(A → T) 和 1764(G → A) 處的雙突變以及 nt1896(G → A) 處的終止突變。 然而，在 2019 年，這些序列中的大多數序列是野生型職位。在 2007 年和 2013 年受試者 TS115 的所有序列中都發現了 nt 2920-3040 之間的缺失，但這些在 2004 年或 2019 年不存在。來自受試者 CC246 的一些序列預測了 2004 年表面蛋白質中的逃逸置換（T123N、G145R），2和 2019 年，但 2007 年的序列都沒有這些變化。總之，HBV突變可能在自然感染中恢復為野生型。臨床醫生應警惕根據突變的存在預測長期預後。

關鍵詞：進化；乙型肝炎病毒;突變;新一代測序；反轉。

版權所有 © 2021。Elsevier B.V. 出版

StephenW

Analysis of entire hepatitis B virus genomes reveals reversion of mutations to wild type in natural infection, a 15 year follow-up study
Qin-Yan Chen  1 , Hui-Hua Jia  2 , Xue-Yan Wang  1 , Yun-Liang Shi  1 , Lu-Juan Zhang  1 , Li-Ping Hu  1 , Chao Wang  1 , Xiang He  3 , Tim J Harrison  4 , J Brooks Jackson  5 , Li Wu  6 , Zhong-Liao Fang  7
Affiliations
Affiliations

    1
    Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China.
    2
    Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China; School of Preclinical Medicine, Guangxi Medical University, 22 ShuangYong Road, Nanning, Guangxi 530021, China.
    3
    Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China.
    4
    Division of Medicine, University College London Medical School, London, UK.
    5
    Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, USA.
    6
    Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, USA.
    7
    Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China. Electronic address: [email protected].

    PMID: 34902556 DOI: 10.1016/j.meegid.2021.105184

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.

Keywords: Evolution; Hepatitis B virus; Mutation; Next-generation sequencing; Reversion.

Copyright © 2021. Published by Elsevier B.V.

StephenW

https://www.sciencedirect.com/sc ... 21004846?via%3Dihub