Characterization of mutations in Hepatitis B virus DNA isolated from Japanese HBsAg-positive blood donors in 2021-2022

Author:

Sedohara Ayako1ORCID,Takahashi Kazuaki1,Arai Keiko1,Arizono Kotaro2,Tuvshinjargal Khulan3,Saito Makoto4,Nakahara Fumio5,Tsutsumi Takeya6,Ikeuchi Kazuhiko4,Adachi Eisuke4,Yotsuyanagi Hiroshi1

Affiliation:

1. The University of Tokyo - Shiroganedai Campus: Tokyo Daigaku - Shiroganedai Campus

2. The University of Tokyo Graduate School of Engineering School of Engineering: Tokyo Daigaku Daigakuin Kogakukei Kenkyuka Kogakubu

3. The University of Tokyo Graduate School of Frontier Sciences: Tokyo Daigaku Daigakuin Shinryoiki Sosei Kagaku Kenkyuka

4. The University of Tokyo Institute of Medical Science Hospital: Tokyo Daigaku Ikagaku Kenkyujo Fuzoku Byoin

5. Jichi Medical University: Jichi Ika Daigaku

6. The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin

Abstract

Abstract Missense mutations in some small-envelope proteins reduce the activity of antibodies. Therefore, it is very important to follow up on the incidence and types of vaccine-escape mutation (VEM) before and after the introduction of the universal hepatitis B vaccination, which was introduced in Japan in 2016. In this study, we isolated hepatitis B virus (HBV) DNA from 58 of 169 hepatitis B surface antigen (HBsAg)-positive blood samples from Japanese blood donors and determined the nucleotide sequence encoding the small-envelope protein. Six of these samples (10%) had VEMs, but no missense mutations such as G145R were detected. Whole-genome sequences were obtained for 29 of the 58 samples, with genotypes A1 in 1 (3%), A2 in 3 (10%), B1 in 9 (31%), B2 in 5 (17%), B4 in 1 (3%), and C2 in 10 (34%) samples. Tenofovir-resistance mutations were detected in two samples (7%). In addition, several core promoter mutations, such as 1762A > T/1764G > A and 1986G > A precore nonsense mutations, which are risk factors for HBV-related chronic liver disease, were detected. These findings provide a baseline for future research and highlight the importance of ongoing monitoring of VEMs and drug-resistance mutations in HBsAg-positive blood donors without HBV antibodies.

Publisher

Research Square Platform LLC

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