Dynamics of Hepatitis B Virus Quasispecies in Association with Nucleos(t)ide Analogue Treatment Determined by Ultra-Deep Sequencing.
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[Background and Aims]: Although the advent of ultra-deep sequencing technology allows for the analysis of heretofore-undetectable minor viral mutants, a limited amount of information is currently available regarding the clinical implications of hepatitis B virus (HBV) genomic heterogeneity. [Methods]: To characterize the HBV genetic heterogeneity in association with anti-viral therapy, we performed ultra-deep sequencing of full-genome HBV in the liver and serum of 19 patients with chronic viral infection, including 14 therapy-naïve and 5 nucleos(t)ide analogue(NA)-treated cases. [Results]: Most genomic changes observed in viral variants were single base substitutions and were widely distributed throughout the HBV genome. Four of eight (50%) chronic therapy-naïve HBeAg-negative patients showed a relatively low prevalence of the G1896A pre-core (pre-C) mutant in the liver tissues, suggesting that other mutations were involved in their HBeAg seroconversion. Interestingly, liver tissues in 4 of 5 (80%) of the chronic NA-treated anti-HBe-positive cases had extremely low levels of the G1896A pre-C mutant (0.0%, 0.0%, 0.1%, and 1.1%), suggesting the high sensitivity of the G1896A pre-C mutant to NA. Moreover, various abundances of clones resistant to NA were common in both the liver and serum of treatment-naïve patients, and the proportion of M204VI mutants resistant to lamivudine and entecavir expanded in response to entecavir treatment in the serum of 35.7% (5/14) of patients, suggesting the putative risk of developing drug resistance to NA. [Conclusion]: Our findings illustrate the strong advantage of deep sequencing on viral genome as a tool for dissecting the pathophysiology of HBV infection.
- 2012-04-16
論文 | ランダム
- 溶融塩溶媒としてのアルカリ金属ハロゲン化物混合塩に関する二つの報告(無機・宇宙・地球・分析化学 トピックス)
- 固体電解質内部の定常状態における化学ポテンシャルのプロフィル(トピックス)
- 各種抗うつ薬の中枢作用
- 慢性糸球体腎炎非透析患者における血漿レニン活性と予後 (慢性糸球体腎炎 その新しい展開(特集)) -- (進展増悪因子とその比重(ネフローゼを除く))
- 生物学的活性測定法 Renin (内分泌機能検査(特集)) -- (ホルモン測定法の進歩 方法の実際と正常値)