title: Nucleotide analogue-resistant mutations in hepatitis B viral genomes found in hepatitis B patients.
abstract: 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.
authors.affiliation: Department of Immunology and Microbiology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Shanghai Jiao Tong University School of Nursing, Shanghai, PR China.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Shanghai Jiao Tong University School of Nursing, Shanghai, PR China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chinese National Human Genome Center, Shanghai, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Immunology and Microbiology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology and Microbiology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Guo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics; D016679:Genome, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil