Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients
Background and Aims: The drug resistance of hepatitis B virus (HBV) originates from mutations within HBV reverse transcriptase (RT) region during the prolonged antiviral therapy. So far, the characteristics of how these mutations distribute and evolve in the process of therapy have not been clarifie...
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1835446 |
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| author | Ya Fu Songhang Wu Yuhai Hu Tianbin Chen Yongbin Zeng Can Liu Qishui Ou |
| author_facet | Ya Fu Songhang Wu Yuhai Hu Tianbin Chen Yongbin Zeng Can Liu Qishui Ou |
| author_sort | Ya Fu |
| collection | DOAJ |
| description | Background and Aims: The drug resistance of hepatitis B virus (HBV) originates from mutations within HBV reverse transcriptase (RT) region during the prolonged antiviral therapy. So far, the characteristics of how these mutations distribute and evolve in the process of therapy have not been clarified yet. Thus we aimed to investigate these characteristics and discuss their contributing factors.Methods: HBV RT region was direct-sequenced in 285 treatment-naive and 214 post-treatment patients. Mutational frequency and Shannon entropy were calculated to identify the specific mutations differing between genotypes or treatment status. A typical putative resistance mutation rtL229V was further studied using in-vitro susceptibility assays and molecular modeling.Results: The classical resistance mutations were rarely detected among treatment-naive individuals, while the putative resistance mutations were observed at 8 AA sites. rtV191I and rtA181T/V were the only resistance mutations identified as genotype-specific mutation. Selective pressure of drug usage not only contributed to the classical resistance mutations, but also induced the changes at a putative resistance mutation site rt229. rtL229V was the major substitution at the site of rt229. It contributed to the most potent suppression of viral replication and reduced the in-vitro drug susceptibility to entecavir (ETV) when coexisting with rtM204V, consistent with the hypothesis based on the molecular modeling and clinical data analysis.Conclusions: The analysis of mutations in RT region under the different circumstances of genotypes and therapy status might pave the way for a better understanding of resistance evolution, thus providing the basis for a rational administration of antiviral therapy. |
| format | Article |
| id | doaj-art-e3770579e14149089a72a6b4d8378c67 |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-e3770579e14149089a72a6b4d8378c672025-08-20T03:08:29ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01912381239310.1080/22221751.2020.1835446Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patientsYa Fu0Songhang Wu1Yuhai Hu2Tianbin Chen3Yongbin Zeng4Can Liu5Qishui Ou6Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaBackground and Aims: The drug resistance of hepatitis B virus (HBV) originates from mutations within HBV reverse transcriptase (RT) region during the prolonged antiviral therapy. So far, the characteristics of how these mutations distribute and evolve in the process of therapy have not been clarified yet. Thus we aimed to investigate these characteristics and discuss their contributing factors.Methods: HBV RT region was direct-sequenced in 285 treatment-naive and 214 post-treatment patients. Mutational frequency and Shannon entropy were calculated to identify the specific mutations differing between genotypes or treatment status. A typical putative resistance mutation rtL229V was further studied using in-vitro susceptibility assays and molecular modeling.Results: The classical resistance mutations were rarely detected among treatment-naive individuals, while the putative resistance mutations were observed at 8 AA sites. rtV191I and rtA181T/V were the only resistance mutations identified as genotype-specific mutation. Selective pressure of drug usage not only contributed to the classical resistance mutations, but also induced the changes at a putative resistance mutation site rt229. rtL229V was the major substitution at the site of rt229. It contributed to the most potent suppression of viral replication and reduced the in-vitro drug susceptibility to entecavir (ETV) when coexisting with rtM204V, consistent with the hypothesis based on the molecular modeling and clinical data analysis.Conclusions: The analysis of mutations in RT region under the different circumstances of genotypes and therapy status might pave the way for a better understanding of resistance evolution, thus providing the basis for a rational administration of antiviral therapy.https://www.tandfonline.com/doi/10.1080/22221751.2020.1835446Hepatitis B virusreverse transcriptaseresistant mutationgenotypephenotype |
| spellingShingle | Ya Fu Songhang Wu Yuhai Hu Tianbin Chen Yongbin Zeng Can Liu Qishui Ou Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients Emerging Microbes and Infections Hepatitis B virus reverse transcriptase resistant mutation genotype phenotype |
| title | Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients |
| title_full | Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients |
| title_fullStr | Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients |
| title_full_unstemmed | Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients |
| title_short | Mutational characterization of HBV reverse transcriptase gene and the genotype-phenotype correlation of antiviral resistance among Chinese chronic hepatitis B patients |
| title_sort | mutational characterization of hbv reverse transcriptase gene and the genotype phenotype correlation of antiviral resistance among chinese chronic hepatitis b patients |
| topic | Hepatitis B virus reverse transcriptase resistant mutation genotype phenotype |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1835446 |
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