A role for glycoprotein C in pseudorabies virus entry that is independent of virus attachment to heparan sulfate and which involves the actin cytoskeleton

Virology. 2003 Mar 1;307(1):12-21. doi: 10.1016/s0042-6822(02)00024-7.

Abstract

Glycoprotein C (gC) of pseudorabies virus, a swine herpesvirus, initiates virus attachment by binding to heparan sulfate (HS) linked to proteoglycans (HSPGs) on the cell surface. This interaction facilitates a required step in virus entry, the binding to a non-HS coreceptor, likely by another viral glycoprotein, gD. We demonstrate that gC has an even more direct role in virus entry than simply promoting adhesion strengthening. A porcine cell line expressing gC trans-complemented the penetration, but not attachment, defect of gC null mutants. In addition, gC promoted the colocalization of cell surface HSPGs and the actin cytoskeleton, suggesting a role for filamentous actin in virus entry. This was supported by results showing that both the engagement of a non-HS coreceptor and entry events subsequent to coreceptor binding were impaired if cells were first treated with an actin depolymerizing agent, cytochalasin D. Our results suggest a model in which gC-HS interactions promote not only virus attachment but also virus entry by usurping the normal properties of HSPGs.

MeSH terms

  • Actins / physiology*
  • Animals
  • Cell Line
  • Cytoskeleton / virology*
  • Heparitin Sulfate / physiology*
  • Herpesvirus 1, Suid / pathogenicity
  • Herpesvirus 1, Suid / physiology*
  • Kidney
  • Pseudorabies / physiopathology
  • Pseudorabies / virology
  • Swine
  • Viral Envelope Proteins / physiology*

Substances

  • Actins
  • Viral Envelope Proteins
  • Heparitin Sulfate