Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naïve Chinese patients.
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.
Liu
Bao-Ming
BM
Department of Microbiology, Peking University Health Science Center, Xueyuan Road 38, Haidian District, 100191 Beijing, China.
Li
Tong
T
Xu
Jie
J
Li
Xiao-Guang
XG
Dong
Jian-Ping
JP
Yan
Ping
P
Yang
Jing-Xian
JX
Yan
Ling
L
Gao
Zhi-Yong
ZY
Li
Wen-Peng
WP
Sun
Xie-Wen
XW
Wang
Yu-Hua
YH
Jiao
Xiu-Juan
XJ
Hou
Chun-Sheng
CS
Zhuang
Hui
H
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
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D012194:RNA-Directed DNA Polymerase