Herpes simplex virus type 1-induced hemagglutination: glycoprotein C mediates virus binding to erythrocyte surface heparan sulfate.
We recently reported that herpes simplex virus type 1 (HSV-1) can cause agglutination of murine erythrocytes (E. Trybala, Z. Larski, and J. Wisniewski, Arch. Virol. 113:89-94, 1990). We now demonstrate that the mechanism of this hemagglutination is glycoprotein C-mediated binding of virus to heparan sulfate moieties at the surface of erythrocytes. Hemagglutination was found to be a common property of all gC-expressing laboratory strains and clinical isolates of HSV-1 tested. Mutants of HSV-1 deficient in glycoprotein C caused no specific hemagglutination, whereas their derivatives transfected with a functional gC-1 gene, thus reconstituting gC expression, regained full hemagglutinating activity. Hemagglutination activity was inhibited by antibodies against gC-1 but not by antibodies with specificity for glycoproteins gB, gD, or gE or by murine antiserum raised against the MP strain of HSV-1, which is gC deficient. Finally, purified gC-1 protein, like whole HSV-1 virions, showed high hemagglutinating activity which was inhibited by heparan sulfate and/or heparin and was completely prevented by pretreatment of erythrocytes with heparitinase, providing evidence that gC-1 mediates hemagglutination by binding to heparan sulfate at the cell surface. Thus, HSV-1-induced hemagglutination is gC-1 dependent and resembles the recently proposed mechanism by which HSV-1 attaches to surface heparans on susceptible cells, providing a simple model for initial events in the virus-cell interaction.
Department of Medicine, University of Minnesota School of Medicine, Minneapolis 554551.
E
E
Trybala
B
B
Svennerholm
T
T
Bergström
S
S
Olofsson
S
S
Jeansson
J L
JL
Goodman
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002459:Cell Fusion; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D006387:Hemagglutination, Viral; D006461:Hemolysis; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism* / Q000494:pharmacology; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011817:Rabbits; D018139:Simplexvirus / Q000254:growth & development / Q000276:immunology*; D012867:Skin / Q000166:cytology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000302:isolation & purification
D000914:Antibodies, Viral; D000956:Antigens, Viral; D006493:Heparin; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; C021349:heparitinsulfate lyase