Differences in the role of glycoprotein C of HSV-1 and HSV-2 in viral binding may contribute to serotype differences in cell tropism

Virology. 1995 Dec 1;214(1):29-39. doi: 10.1006/viro.1995.9957.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Chlorocebus aethiops
  • Complement System Proteins / immunology
  • DNA Primers
  • Heparitin Sulfate / metabolism
  • Herpesvirus 1, Human / classification
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 1, Human / metabolism*
  • Herpesvirus 2, Human / classification
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / immunology
  • Herpesvirus 2, Human / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Neutralization Tests
  • Receptors, Virus / metabolism
  • Serotyping
  • Species Specificity
  • Tumor Cells, Cultured
  • Vero Cells
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*


  • DNA Primers
  • Receptors, Virus
  • Viral Envelope Proteins
  • glycoprotein C, herpes simplex virus type 2
  • glycoprotein gC, herpes simplex virus type 1
  • Complement System Proteins
  • Heparitin Sulfate