title: Characterization of contrasting features between hepatitis B virus genotype A and genotype D in small envelope protein expression and surface antigen secretion.
abstract: Hepatitis B virus (HBV) genotypes A and D are prevalent in many parts of the world and show overlapping geographic distributions. We amplified the entire HBV genome from sera of patients with genotypes A and D and generated overlength constructs for transient transfection into Huh7 or HepG2 cells. Genotype D clones were associated with less HBsAg in culture supernatant and even less intracellular HBsAg. They produced less 2.1-kb RNA due to a weaker SPII promoter. Chimeric promoter constructs identified three divergent positions as most critical, and their exchange reversed extracellular HBsAg phenotype. The S protein of genotype D was more efficient at secretion, while its L protein possessed greater inhibitory effect. Swapping the S gene diminished genotypic difference in intracellular S protein but widened the difference in secreted HBsAg. In conclusion, HBV genotypes A and D differ in S protein expression, secretion and modulation by L protein.
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.affiliation: Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Tamako
authors.initials: T
authors.lastname: Garcia
authors.affiliation: Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Haodi
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Jisu
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, USA. Electronic address: shuping_tong_md@brown.edu.
authors.forename: Shuping
authors.initials: S
authors.lastname: Tong
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D005838:Genotype; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins
keywords: Genotype; Hepatitis B surface antigen; Hepatitis B virus; Large envelope protein; SPII promoter; Small envelope protein