Nucleotide analogue-resistant mutations in hepatitis B viral genomes found in hepatitis B patients

作者：Fan, Jiyun; Zhang, Yaqing; Xiong, Hui; Wang, Ying; Guo, Xiaokui^*

来源：Journal of General Virology, 2015, 96(Pt_3): 663-670.

DOI：10.1099/jgv.0.000010

• HBV DRUG-RESISTANCE
• REVERSE-TRANSCRIPTASE SEQUENCES
• TREATMENT-NAIVE PATIENTS
• ANTIVIRAL RESISTANCE
• GENOTYPE-C
• LAMIVUDINE RESISTANCE
• ENTECAVIR RESISTANCE
• CHINESE PATIENTS
• IN-VITRO
• VIRUS

Chronic hepatitis B (CHB) is treated with nucleos(t)ide analogues (NAs). The reverse transcriptase (RT) region in the hepatitis B virus (HBV) genome mutates to resist NA treatment, yet the RT mutations have not been well characterized. Furthermore, the HBV genotype might influence RT sequence evolution, NA resistance (NAr) mutation patterns and drug resistance development. We examined 42 NAr mutation sites in 169 untreated and 131 NA-treated CHB patient samples. Patients were identified with HBV-B and HBV-C genotype infections, with a higher prevalence and mutation frequency of HBV-C than HBV-B. Seventeen reported NAr mutation sites and 13 novel mutations were detected. NAr-related mutation prevalence was significantly higher in NA-treated versus untreated patients. Primary antiviral-resistant mutants only existed in NA-treated patients. Sequencing data revealed seven HBV-C-specific mutations and three HBV-B-specific mutations. In conclusion, NA treatment and HBV genotype might constitute the selection basis and promote NA-resistant HBV strain evolution under antiviral therapy.

• 出版日期2015-3
• 单位上海交通大学; 上海人类基因组研究中心; 河北医科大学