A strong conservative tendency in HBV transcriptase (RT): a majority of natural RT mutations derived from the S gene

作者：Li, Hu; Song, Xiao-Fei; Hu, Ting-Ting; Ren, Hong; Hu, Peng^*

来源：Liver International, 2016, 36(7): 963-970.

DOI：10.1111/liv.13051

• chronic HBV infection
• chronic hepatitis B
• Mutation
• reverse transcriptase

Background & AimsLittle is known about natural mutations in the HBV reverse transcriptase (RT) region. Our study aimed to characterize the natural RT mutation along the natural course of chronic Hepatitis B (CHB).
MethodsSixty CHB patients (immune-tolerant phase, IT, n = 20; immune-active phase, IA, n = 20 and inactive carriers phase, IC, n = 20) were selected from the Focal study, including 25 subjects with median 18 months follow-up. Mutations were evaluated at both RT and main S protein encoding region by clone-based sequencing.
ResultsThe HBV RT quasispecies had significant lower heterogeneity in IT than IA and IC phases (P < 0.05), but not between IA and IC phases (P > 0.05). Limited heterogeneity over time was further confirmed in a longitudinal study. Locations of RT mutations were primarily located in the interdomians and the lowest in functional domains in each phase. Mutations in human leukocyte antigen (HLA) I epitopes (IT, 0.95%; IA, 1.31%; IC, 1.28%, P < 0.05) and HLA II epitopes (IT, 0.70%; IA, 0.90%; IC, 1.45%, P < 0.01) varied significantly over time. More frequent mutations were detected in the ORF of S gene from the same clones (HBsAg vs. RT: IT, 75 vs. 45; IA, 83 vs. 64; IC, 80 vs. 65). The majority of RT mutations were shared with genetic changes in the main S gene.
ConclusionsOur findings suggested that HBV RT showed a strong conservative tendency and a majority of their natural mutations were derived from the same genetic changes in the S gene.

• 出版日期2016-7
• 单位重庆医科大学