Characterization of hepatitis B virus reverse transcriptase sequences in Chinese treatment naive patients

Background and Aims: 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). Conclusion: Primarily antiviral resistance related mutant strains do exist in treatment naive 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.