title: Hepatitis B surface antigen levels and sequences of natural hepatitis B virus variants influence the assembly and secretion of hepatitis d virus.
abstract: Various domains of hepatitis B surface antigen (HBsAg) are essential for the assembly and secretion of hepatitis D virus (HDV). This study investigated the influences of the levels and sequences of HBsAg of naturally occurring HBV variants on the assembly and secretion of HDV. Six hepatitis B virus (HBV)-producing plasmids (three genotype B and three genotype C) and six HBsAg expression plasmids that expressed various HBsAg levels were constructed from the sera of HDV-infected patients. These plasmids were cotransfected with six expression plasmids of HDV of genotype 1, 2, or 4 into the Huh-7 hepatoma cell line. Serum HBsAg and HBV DNA levels were correlated with HDV RNA levels and outcomes of chronic hepatitis D (CHD) patients. The secretion of genotype 1, 2, or 4 HDV generally correlated with HBsAg levels but not with HBV genotypes or HBV DNA levels. Swapping and residue mutagenesis experiments of HBsAg-coding sequences revealed that the residue Pro-62 in the cytosolic domain-I affects the assembly and secretion of genotype 2 and 4 HDV and not those of genotype 1. The pre-S2 N-terminal deletion HBV mutant adversely affects secretion of the three HDV genotypes. In patients, serum HDV RNA levels correlated with HBsAg levels but not with HBV DNA levels. Viremia of HDV or HBV correlated with poor outcomes. In conclusion, the assembly and secretion of HDV were influenced by the amounts and sequences of HBsAg. For an effective treatment of CHD, reduction of HBsAg production in addition to the suppression of HBV and HDV replication might be crucial.
authors: Department of Medical Research and Education, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming University, 201, Shih-Pai Road, Sec. 2, Taipei 11217, Taiwan.
authors: Hsuan Hui
authors: HH
authors: Shih
authors: King-Song
authors: KS
authors: Jeng
authors: Wan-Jr
authors: WJ
authors: Syu
authors: Yi-Hsiang
authors: YH
authors: Huang
authors: Chien-Wei
authors: CW
authors: Su
authors: Wei-Li
authors: WL
authors: Peng
authors: I-Jane
authors: IJ
authors: Sheen
authors: Jaw-Ching
authors: JC
authors: Wu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics*; D003698:Hepatitis Delta Virus / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D017386:Sequence Homology, Amino Acid; D019065:Virus Assembly
chemical_list: D017931:DNA Primers; D006514:Hepatitis B Surface Antigens