Differences in the role of glycoprotein C of HSV-1 and HSV-2 in viral binding may contribute to serotype differences in cell tropism.
Heparan sulfate serves as a receptor for several herpesviruses. For herpes simplex virus 1 (HSV-1), pseudorabies virus, and bovine herpesvirus 1, glycoprotein C homologues have been shown to mediate the binding to cell-surface heparan sulfate. It has been assumed that glycoprotein C of HSV-2 (gC-2) plays a similar role in HSV-2 entry, but this has not been established experimentally. We first determined, using heparin-affinity chromatography, that gC-2 is a heparin-binding glycoprotein. To examine the role of gC-2 in HSV-2 infection, we constructed a gC-2 deletion mutant, HSV-2(G)gC-. In contrast to results obtained for the other alpha herpesviruses, we found that the HSV-2(G)gC- virus showed no loss in specific binding activity (particles bound/cell) or specific infectivity (PFU/particle) compared to the parental wild-type virus. Moreover, while gC-1 mutants show a marked lag in the rate of viral penetration, the gC-2-deletion virus did not. We did find that gC-2, like gC-1, protects virus from complement-mediated neutralization. These results suggest that, in contrast to HSV-1, gC-2 does not play the key role in viral binding. The major role of gC-2 may be to protect virus from complement-mediated neutralization. We speculate that serotype differences in the contribution of gC to viral binding may contribute to serotype differences in cell tropism.
Gerber
S I
SI
Section of Pediatric Infectious Diseases, University of Chicago, Illinois 60637-1470, USA.
Belval
B J
BJ
Herold
B C
BC
D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D003165:Complement System Proteins / Q000276:immunology; D017931:DNA Primers; D006497:Heparan Sulfate / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009500:Neutralization Tests; D011991:Receptors, Virus / Q000378:metabolism; D012703:Serotyping; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D003165:Complement System Proteins; D017931:DNA Primers; D006497:Heparan Sulfate; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C048232:glycoprotein C, herpes simplex virus type 2; C038535:glycoprotein gC, herpes simplex virus type 1