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 ct 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 go 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 go to viral binding may contribute to serotype differences in cell tropism. (C) 1995 Academic Press, Inc.