title: A role for glycoprotein C in pseudorabies virus entry that is independent of virus attachment to heparan sulfate and which involves the actin cytoskeleton.
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.
authors.affiliation: Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: Cary A
authors.initials: CA
authors.lastname: Rue
authors.forename: Patrick
authors.initials: P
authors.lastname: Ryan
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000821:virology*; D006497:Heparan Sulfate / Q000502:physiology*; D011558:Herpesvirus 1, Suid / Q000472:pathogenicity / Q000502:physiology*; D007668:Kidney; D011557:Pseudorabies / Q000503:physiopathology / Q000821:virology; D013552:Swine; D014759:Viral Envelope Proteins / Q000502:physiology*
chemical_list: D000199:Actins; D006497:Heparan Sulfate; D014759:Viral Envelope Proteins