title: Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naïve Chinese patients.
abstract: Full-length hepatitis B virus (HBV) reverse transcriptase (RT) sequences were amplified and sequenced among 192 nucleos(t)ide analogue (NA)-naïve Chinese patients with chronic hepatitis B. Deduced amino acids (AAs) at 42 previously reported potential NA resistance (NAr) mutation positions in RT region were analyzed. Patients were found with either B-genotype (28.65%) or C-genotype (71.35%) infections. Rt53, rt91, rt124, rt134, rt221, rt224, rt238 and rt256 were identified as B- and C-genotype-dependent polymorphic AA positions. AA substitutions at 11 classical NAr mutation positions, i.e. rt80, rt169, rt173, rt180, rt181, rt184, rt194, rt202, rt204, rt236 and rt250, were not detected. However, potential NAr mutations were found in 30.73% (59/192) isolates, which involved 18 positions including rt53, rt207, rt229, rt238 and rt256, etc. The concomitant AA changes of HBsAg occurred in 16.67% (32/192) isolates including sG145R mutation. One-third of mutation positions were located in functional RT domains (e.g. rt207 and rt233), A-B interdomains (overlapping HBsAg 'a' determinant and showing most concomitant immune-associated mutations) and non-A-B interdomains (e.g. rt191 and rt213), respectively. Genotypes B and C each showed several preferred positions to mutate. These results might provide insights into understanding the evolution and selection basis of NAr HBV strains under antiviral therapy.
authors.affiliation: Department of Microbiology, Peking University Health Science Center, Xueyuan Road 38, Haidian District, 100191 Beijing, China.
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Li
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Dong
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.forename: Jing-Xian
authors.initials: JX
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Gao
authors.forename: Wen-Peng
authors.initials: WP
authors.lastname: Li
authors.forename: Xie-Wen
authors.initials: XW
authors.lastname: Sun
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Jiao
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Hou
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D002681:China; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D012194:RNA-Directed DNA Polymerase