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.
Section of Pediatric Infectious Diseases, University of Chicago, Illinois 60637-1470, USA.
S I
SI
Gerber
B J
BJ
Belval
B C
BC
Herold
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