title: Pro-205 of large hepatitis delta antigen and Pro-62 of major hepatitis B surface antigen influence the assembly of different genotypes of hepatitis D virus.
abstract: Hepatitis B surface antigen (HBsAg) is essential for the assembly and infection of hepatitis D virus (HDV). The assembly efficiency of genotype 1 HDV is higher than that of genotype 2, whilst the P62L substitution of major HBsAg further compromises the assembly of genotype 2 and 4 HDV. This study investigated the influence of proline residues in the carboxyl end of the large hepatitis delta antigen (HDAg-L) on the assembly of HDV of different genotypes. Expression vectors containing the HDAg-L gene or full-length HDV genome of genotype 1, 2 or 4 were co-transfected with plasmids expressing HBsAg proteins that bore either proline or leucine residues at position 62. Of the eight HDV genotypes, only genotype 1 has Pro-205 in HDAg-L, whereas genotypes 2 and 4 have Arg-205. The Arg-205 to Pro-205 substitution in HDV-2 and -4 markedly increased the assembly efficiencies of HDAg-L and whole HDV genomes, even in the presence of HBsAg with Leu-62. In contrast, secretion of genotype 1 HDV or HDAg-L was reduced significantly when arginine or alanine replaced Pro-205. When HBsAg contained Pro-62, the influence of Pro-205 on assembly decreased. In conclusion, both Pro-205 of the HDAg-L and Pro-62 of the major HBsAg play critical roles in the assembly of HDV of different genotypes. The presence of Pro-205 in genotype 1 HDV may account for its higher assembly efficiencies and wider distribution.
authors: Department of Medical Research and Education, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors: Hsuan Hui
authors: HH
authors: Shih
authors: Chiaho
authors: C
authors: Shih
authors: Hsei-Wei
authors: HW
authors: Wang
authors: Chien-Wei
authors: CW
authors: Su
authors: I-Jane
authors: IJ
authors: Sheen
authors: Jaw-Ching
authors: JC
authors: Wu
mesh_terms: D019943:Amino Acid Substitution; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000502:physiology*; D003698:Hepatitis Delta Virus / Q000145:classification / Q000235:genetics / Q000502:physiology*; D035923:Hepatitis delta Antigens / Q000737:chemistry / Q000502:physiology*; D011392:Proline; D017434:Protein Structure, Tertiary; D019065:Virus Assembly
chemical_list: D006514:Hepatitis B Surface Antigens; D035923:Hepatitis delta Antigens; C442244:hepatitis delta virus large antigen; D011392:Proline