PMID- 26707356 OWN - NLM STAT- MEDLINE DCOM- 20171116 LR - 20220317 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 36 IP - 7 DP - 2016 Jul TI - A strong conservative tendency in HBV transcriptase (RT): a majority of natural RT mutations derived from the S gene. PG - 963-70 LID - 10.1111/liv.13051 [doi] AB - BACKGROUND & AIMS: Little 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). METHODS: Sixty 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. RESULTS: The 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. CONCLUSIONS: Our 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. CI - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Li, Hu AU - Li H AD - Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Song, Xiao-Fei AU - Song XF AD - Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Hu, Ting-Ting AU - Hu TT AD - Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Ren, Hong AU - Ren H AD - Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Hu, Peng AU - Hu P AD - Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160108 PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (DNA, Viral) RN - EC 2.7.7.49 (RNA-Directed DNA Polymerase) SB - IM MH - Adult MH - China MH - DNA, Viral/*genetics MH - Female MH - Genetic Heterogeneity MH - Genotype MH - Hepatitis B virus/enzymology/*genetics MH - Hepatitis B, Chronic/*virology MH - Humans MH - Longitudinal Studies MH - Male MH - Mutation MH - RNA-Directed DNA Polymerase/*genetics MH - Young Adult OTO - NOTNLM OT - Mutation OT - chronic HBV infection OT - chronic hepatitis B OT - reverse transcriptase EDAT- 2015/12/29 06:00 MHDA- 2017/11/29 06:00 CRDT- 2015/12/29 06:00 PHST- 2015/05/22 00:00 [received] PHST- 2015/12/11 00:00 [accepted] PHST- 2015/12/29 06:00 [entrez] PHST- 2015/12/29 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] AID - 10.1111/liv.13051 [doi] PST - ppublish SO - Liver Int. 2016 Jul;36(7):963-70. doi: 10.1111/liv.13051. Epub 2016 Jan 8.