https://scholars.lib.ntu.edu.tw/handle/123456789/568276
標題: | Whole genome deep sequencing analysis of viral quasispecies diversity and evolution in HBeAg seroconverters | 作者: | Lin, Su Ru Yang, Ta Yu Peng, Cheng Yuan Lin, You Yu Dai, Chia Yen HURNG-YI WANG TUNG-HUNG SU TAI-CHUNG TSENG Liu, I. Jung Cheng, Huei Ru Shen, Yueh Chi Wu, Fang Yi CHUN-JEN LIU DING-SHINN CHEN PEI-JER CHEN HUNG-CHIH YANG JIA-HORNG KAO |
關鍵字: | Chronic hepatitis B | HBeAg seroconversion | Intra-host single nucleotide variants;Chronic hepatitis B; HBeAg seroconversion; Intra-host single nucleotide variants | 公開日期: | 1-六月-2021 | 卷: | 3 | 期: | 3 | 來源出版物: | JHEP Reports | 摘要: | Background & Aims: We aimed to investigate how viral quasispecies of the HBV whole genome evolves and diversifies in response to HBeAg seroconversion and viral control utilising next-generation sequencing (NGS). Methods: Fifty HBeAg-positive chronic hepatitis B patients, including 18 treatment-naïve and 32 interferon (IFN)-treated individuals, were recruited. Serial HBV whole genomes in serum were analysed by NGS to determine sequence characteristics and viral quasispecies. Results: HBV quasispecies diversity, measured by nucleotide diversity, was negatively correlated with viral load and hepatitis activity. Spontaneous HBeAg seroconverters exhibited significantly greater viral quasispecies diversity than treatment-naïve non-seroconverters from >1 year before seroconversion (0.0112 vs. 0.0060, p <0.01) to >1 year after seroconversion (0.0103 vs. 0.0068, p <0.01). IFN-induced HBeAg seroconverters tended to have higher viral genetic diversity than non-seroconverters along with treatment. Particularly, the IFN responders, defined as IFN-induced HBeAg seroconversion with low viraemia, exhibited significantly greater genetic diversity of whole HBV genome at 6 months post-IFN treatment than IFN non-responders (0.0148 vs. 0.0106, p = 0.048). Moreover, spontaneous HBeAg seroconverters and IFN responders exhibited significantly higher evolutionary rates and more intra-host single-nucleotide variants. Interestingly, in spontaneous HBeAg seroconverters and IFN responders, there were distinct evolutionary patterns in the HBV genome. Conclusions: Higher HBV quasispecies diversity is associated with spontaneous HBeAg seroconversion and IFN-induced HBeAg seroconversion with low viraemia, conferring a favourable clinical outcome. Lay summary: HBeAg seroconversion is a landmark in the natural history of chronic HBV infection. Using next-generation sequencing, we found that the nucleotide diversity of HBV was negatively correlated with viral load and hepatitis activity. Patients undergoing HBeAg seroconversion had more diverse HBV genomes and a faster viral evolution rate. Our findings suggest HBeAg seroconversion is driven by host selection pressure, likely immune selection pressure. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/568276 | ISSN: | 25895559 | DOI: | 10.1016/j.jhepr.2021.100254 | SDG/關鍵字: | hepatitis B(e) antigen; interferon; adult; Article; chronic hepatitis B; clinical article; clinical outcome; cohort analysis; controlled study; female; genetic variability; hepatitis B; high throughput sequencing; human; male; nonhuman; priority journal; quasispecies; seroconversion; single nucleotide polymorphism; T lymphocyte; viral evolution; viremia; virus genome; virus load; whole genome sequencing |
顯示於: | 臨床醫學研究所 |
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