TY - JOUR
T1 - Differences in the Role of Glycoprotein C of HSV-1 and HSV-2 in Viral Binding May Contribute to Serotype Differences in Cell Tropism
AU - Gerber, Susan I.
AU - Belval, Brian J.
AU - Herold, Betsy C.
N1 - Funding Information:
We are grateful to C. Brandt, P. Schaffer, and B. Roizman for providing viral strains, P. Spear for providing plasmids and antisera, and P. Spear and the members of her laboratory and B. Roizman and the members of his laboratory for advice. S.I.G. is the recipient of a 1993–1995 American Social Health Association Postdoctoral Research Fellowship in Sexually Transmitted Diseases and is also supported by Public Health Service Grant AI-00172. B.C.H. is supported by a Junior Faculty Award from the American Cancer Society and a Career Development Award from the Schweppe Foundation.
PY - 1995/12/1
Y1 - 1995/12/1
N2 - 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 α 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.
AB - 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 α 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.
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U2 - 10.1006/viro.1995.9957
DO - 10.1006/viro.1995.9957
M3 - Article
C2 - 8525631
AN - SCOPUS:0028860464
SN - 0042-6822
VL - 214
SP - 29
EP - 39
JO - Virology
JF - Virology
IS - 1
M1 - 79957
ER -