Glycine decarboxylase mediates a postbinding step in duck hepatitis B virus infection.
Envelope protein precursors of many viruses are processed by a basic endopeptidase to generate two molecules, one for receptor binding and the other for membrane fusion. Such a cleavage event has not been demonstrated for the hepatitis B virus family. Two binding partners for duck hepatitis B virus (DHBV) pre-S envelope protein have been identified. Duck carboxypeptidase D (DCPD) interacts with the full-length pre-S protein and is the DHBV docking receptor, while duck glycine decarboxylase (DGD) has the potential to bind several deletion constructs of the pre-S protein in vitro. Interestingly, DGD but not DCPD expression was diminished following prolonged culture of primary duck hepatocytes (PDH), which impaired productive DHBV infection. Introduction of exogenous DGD promoted formation of protein-free viral genome, suggesting restoration of several early events in viral life cycle. Conversely, blocking DGD expression in fresh PDH by antisense RNA abolished DHBV infection. Moreover, addition of DGD antibodies soon after virus binding reduced endogenous DGD protein levels and impaired production of covalently closed circular DNA, the template for DHBV gene expression and genome replication. Our findings implicate this second pre-S binding protein as a critical cellular factor for productive DHBV infection. We hypothesize that DCPD, a molecule cycling between the cell surface and the trans-Golgi network, targets DHBV particles to the secretary pathway for proteolytic cleavage of viral envelope protein. DGD represents the functional equivalent of other virus receptors in its interaction with processed viral particles.
Li
Jisu
J
The Liver Research Center, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, USA. Ji_Su_Li_MD@Brown.edu
Tong
Shuping
S
Lee
Hong Bock
HB
Perdigoto
Ana Luisa
AL
Spangenberg
Hans Christian
HC
Wands
Jack R
JR
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism; D002478:Cells, Cultured; D004372:Ducks; D050841:Glycine Dehydrogenase (Decarboxylating); D018347:Hepadnaviridae Infections / Q000821:virology*; D015611:Hepatitis B Virus, Duck / Q000472:pathogenicity*; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D022781:Hepatocytes / Q000201:enzymology / Q000821:virology; D014774:Virulence
D000594:Amino Acid Oxidoreductases; D050841:Glycine Dehydrogenase (Decarboxylating); D002268:Carboxypeptidases