Impacts of HBV rtH55R Polymerase Substitution on Viral Replication and rtM204I/V Resistance to Nucleoside/Nucleotide Antiviral Drugs. Issue 1 (January 2018)

• Record Type: Journal Article
• Authors: Xiang, Kuan-Hui; Zhao, Cheng-Yu; Wang, Shuai; Li, Yao; Su, Ming-Ze; Wang, Qiang-Yi; Xu, Xi-Zhan; Deng, Juan; Zhuang, Hui; Li, Tong
• Is Part Of: Antiviral therapy. Volume 23:Issue 1(2018)
• Page Start: 33
• Page End: 42
• Publication Date: 2018-01
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP3170
• Languages: English
• ISSNs: 1359-6535

Abstract

Background: High genetic variability at the reverse transcriptase (RT) region of HBV could confer resistance to nucleoside/nucleotide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUC resistance. Methods: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analysed to identify potential RT substitutions related to NUC resistance. In vitro studies without and with NUCs were performed in a HepG2 cell line transfected by clones with RT harbouring wild-type or substituted AA(s) of interest. Results: Among 261 NUC-treated CHB patients, we found a high detection rate of rtM204I/V substitution (30.7% [80/261]). We identified a new substitution of rtH55R, and its detection rate had a significantly increasing trend from 3.8% (9/240) in the untreated group to 7.2% (13/181) or 33.8% (27/80) in the treated group with rtM204 or with rtM204I/V substitutions ( P <0.0001). In vitro studies showed that rtH55R had a similar HBV DNA level compared to wild type. The rtH55R+rtM204I clone had a significantly better replication capacity than the rtM204I clone without NUCs ( P <0.05). The replication capacity of the rtM204I clone was found to significantly decrease under lamivudine treatment, but this was not found in the rtH55R+rtM204I clone. Conclusions: We identified a new HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is frequently found in combination with rtM204I/V substitution under NUC treatment. In vitro studies suggest that it might play some replication compensatory role in rtM204I mutants under lamivudine treatment.