Characterization of hepatitis B virus reverse transcriptase sequences in Chinese treatment naive patients.
OBJECTIVE
The hepatitis B virus (HBV) reverse transcriptase (RT) plays an important role in viral replication. The aim of the present study was to characterize profiles of the RT region and to construct a database for further studies.


METHODS
Serum samples were obtained from 328 treatment naive patients chronically infected with HBV in five Chinese cities. Mutation status, genotypes and deep sequence analysis were carried out by amplifying and sequencing the RT region.


RESULTS
The base usage in the RT region differed at the mono- and dinucleotide level and thymidine dominated. The higher the variability of the strain was, the more it replicated. No significant clustering was found between our HBV RT sequences and those isolated 10 years ago (achieved from genebank). Nucleotide analogue resistance related mutants exist. The M204V/I mutation was found in 1.8% of the strains, 1.2% had L180M+ M204V/I, 0.6% had A181T/V, and only one had all three mutations. Minor strain mutants were found in 9.3% of the samples studied. The genotype B patients made up 36.6% (88.7% B2) and were mostly found in southern China, 63.4% (92.2% C2) were genotype C, and only one was genotype D. The average age of HBeAg positive genotype B patients was 29.5 +/- 10.4 years, for genotype C it was 36.1 +/- 10.9 (P < 0.001).


CONCLUSIONS
Primarily antiviral resistance related mutant strains do exist in treatment naïve patients. Without antiviral pressure, HBV strains evolved at a normal speed. In depth sequence analysis implied that viral replication might be correlated with its variability, which needs to be further investigated.
Han
Yue
Y
Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Huang
Li Hua
LH
Liu
Chuan Miao
CM
Yang
Shu
S
Li
Juan
J
Lin
Zhi Mei
ZM
Kong
Xiao Fei
XF
Yu
De Min
DM
Zhang
Dong Hua
DH
Jin
Gen Di
GD
Lu
Zhi Meng
ZM
Gong
Qi Ming
QM
Zhang
Xin Xin
XX
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D001482:Base Composition; D002681:China / Q000453:epidemiology; D019295:Computational Biology; D004279:DNA, Viral / Q000097:blood; D030541:Databases, Genetic; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy / Q000208:ethnology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use; D010641:Phenotype; D010802:Phylogeny; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D017211:Treatment Failure; D014779:Virus Replication / Q000235:genetics; D055815:Young Adult
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D012194:RNA-Directed DNA Polymerase; D000225:Adenine