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.
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.
Shih
Hsuan Hui
HH
Department of Medical Research and Education, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Shih
Chiaho
C
Wang
Hsei-Wei
HW
Su
Chien-Wei
CW
Sheen
I-Jane
IJ
Wu
Jaw-Ching
JC
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
D006514:Hepatitis B Surface Antigens; D035923:Hepatitis delta Antigens; C442244:hepatitis delta virus large antigen; D011392:Proline