The arginine-rich carboxy-terminal domain of the hepatitis B virus core protein mediates attachment of nucleocapsids to cell-surface-expressed heparan sulfate.
Binding of hepatitis B virus nucleocapsids to mouse B cells leads to production of nucleocapsid-specific antibodies, class II presentation of peptides and the generation of T helper-1 immunity. This T-cell-independent activation of B cells is thought to result from cross-linking of cell-surface immunoglobulin molecules, if these contain a specific motif in the framework region 1-complementarity determining region 1 junction. In the present study, it was observed that nucleocapsids bound to different B-cell lines, an interaction that was not dependent on cell-surface-expressed immunoglobulins. Furthermore, binding to several non-B-cell lines was observed. Capsids that lacked the carboxy-terminal protamine-like domains did not bind to cells. Treatment of nucleocapsids with ribonucleases enhanced the attachment of nucleocapsids to cells. Various soluble glycosaminoglycans inhibited attachment of nucleocapsids, while treatment of cells with heparinase I also reduced binding. These observations demonstrated that the arginine-rich protamine-like regions of the core proteins are responsible for the attachment of nucleocapsids to glycosaminoglycans expressed on the plasma membranes of cells.
Vanlandschoot
Peter
P
Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Van Houtte
Freya
F
Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Serruys
Benedikte
B
Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Leroux-Roels
Geert
G
Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
D000818:Animals; D001120:Arginine; D002460:Cell Line; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D019763:Heparin Lyase / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D019590:Nucleocapsid Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis; D012260:Ribonucleases / Q000494:pharmacology
D001120:Arginine; D006025:Glycosaminoglycans; D019763:Heparin Lyase; D006497:Heparan Sulfate; D006512:Hepatitis B Core Antigens; D019590:Nucleocapsid Proteins; D011994:Recombinant Proteins; D012260:Ribonucleases