A short sequence within domain C of duck carboxypeptidase D is critical for duck hepatitis B virus binding and determines host specificity.
Virus-cell surface receptor interactions are of major interest. Hepadnaviruses are a family of partially double-stranded DNA viruses with liver tropism and a narrow host range of susceptibility to infection. At least in the case of duck hepatitis B virus (DHBV), host specificity seems controlled partly at the receptor level. The middle portion in the pre-S region of the viral large envelope protein binds specifically to duck carboxypeptidase D (DCPD) but not to its human or chicken homologue. Although domain C of DCPD is implicated in ligand binding, the exact pre-S contact site remains to be determined. We prepared and tested a panel of chimeric constructs consisting of DCPD and human carboxypeptidase D (HCPD). Our results indicate that a short region at the N terminus of domain C (residues 920 to 949) is critical to DHBV binding and is a major determinant for the host specificity of DHBV infection. Replacing this region of the DCPD molecule with its human homologue abolished the DHBV interaction, whereas introducing this DCPD sequence into HCPD conferred efficient DHBV binding. Extensive analysis of site-directed mutants revealed that both conserved and nonconserved residues were important for the pre-S interaction. There were primary sequence variations and secondary structural differences that contributed to the inability of HCPD to bind the DHBV pre-S domain.
Spangenberg
H C
HC
Liver Research Center, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
Lee
H B
HB
Li
J
J
Tan
F
F
Skidgel
R
R
Wands
J R
JR
Tong
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002268:Carboxypeptidases / Q000737:chemistry* / Q000502:physiology; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology*; D013329:Structure-Activity Relationship
D011991:Receptors, Virus; D002268:Carboxypeptidases; C078874:carboxypeptidase D