Alternative entry receptors for herpes simplex virus and their roles in disease.

Either herpesvirus entry mediator (HVEM, TNFRSF14) or nectin-1 (PVRL1) is sufficient for herpes simplex virus (HSV) infection of cultured cells. The contribution of individual receptors to infection in vivo and to disease is less clear. To assess this, Tnfrsf14(-/-) and/or Pvrl1(-/-) mice were challenged intravaginally with HSV-2.

Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B.

Previous studies have shown that the initial interaction of herpes simplex virus (HSV) with cells is binding to heparan sulphate and that HSV-1 glycoprotein C (gC) is principally responsible for this binding. Although gC-negative viral mutants are impaired for binding and entry, they retain significant infectivity. The purpose of the studies reported here was to explore the requirements for infectivity of gC-negative HSV-1 mutants.

Single amino acid substitutions in gD of herpes simplex virus 1 confer resistance to gD-mediated interference and cause cell-type-dependent alterations in infectivity.

Previous studies have shown that cell-associated herpes simplex virus (HSV) glycoprotein gD can interfere with infection of the cells by HSV and other alphaherpesviruses and that HSV mutants resistant to this gD-mediated interference can be isolated. Here we report that HSV mutants selected for resistance to gD-mediated interference are altered in specific infectivity for cells that do not express gD. Two independently derived mutants were shown to be impaired in ability to infect HEp-2 cells and enhanced in ability to infect Chinese hamster ovary cells, compared with the wild-type parental strain.