title: Biological characteristics comparison of HBV rtA181T mutants with truncated or substituted HBsAg expression in vitro and in vivo model systems.
abstract: The hepatitis B virus(HBV) polymerase rtA181T mutation is selected during long-term antiviral therapy. As the polymerase gene completely overlaps with the envelope (S) gene, HBV rtA181T mutation also carries sW172 mutations. In this study, we investigated whether there were biological differences between rtA181T/sW172* (coding truncated HBsAg) and rtA181T/sW172L (coding substituted HBsAg) mutants. In cell experiments, a slight decline of viral replication was observed in both two mutants as compared to wild-type strains, but the levels of supernatant HBsAg and HBV DNA in rtA181T/sW172* were significantly lower than those in rtA181T/sW172L transfected cells. In animal experiments, we were amazed to find that viral replication in rtA181T/sW172* mutant increased and maintained significantly longer than that in rtA181T/sW172L mutant, while no significant difference was observed between rtA181T/sW172L and wild-type strains. Compared with wild-type strains, there were intracellular accumulations of HBsAg and HBcAg in rtA181/sW172* but none in rtA181/sW172L mutant strains. Importantly, we also found that truncated HBsAg could increase the activity of HBV core promoter, but substituted HBsAg could not. In summary, the characteristics of above two rtA181T mutants mentioned above were significantly different, and it is necessary and important for us to distinguish sW172* truncated mutation from sW172L substituted mutation.
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: En-Qiang
authors.initials: EQ
authors.lastname: Chen
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Meng-Lan
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lan-Lan
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Liu
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.|Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000097:blood / Q000378:metabolism; D056945:Hep G2 Cells; D006512:Hepatitis B Core Antigens / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000201:enzymology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D012194:RNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D012194:RNA-Directed DNA Polymerase