title: A strong conservative tendency in HBV transcriptase (RT): a majority of natural RT mutations derived from the S gene.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
mesh_terms: D000328:Adult; D002681:China; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012194:RNA-Directed DNA Polymerase
keywords: Mutation; chronic HBV infection; chronic hepatitis B; reverse transcriptase