Contributions of gD receptors and glycosaminoglycan sulfation to cell fusion mediated by herpes simplex virus 1

Two cell surface proteins (nectin-1/HveC and nectin-2/HveB) shown previousl y to serve as receptors for the entry of herpes simplex virus 1 (HSV-1) wil d-type and/or mutant strains were found to serve also as receptors for HSV- I-induced cell fusion. Transfection with genomic DNA from a syncytial HSV-1 strain encoding wild-type go resulted in fusion of Chinese hamster ovary ( CHO) cells expressing nectin-1 but not of cells expressing nectin-2. In con trast, transfection with DNA from a related HSV-1 strain encoding the mutan t Rid1 form of go resulted in fusion of CHO cells expressing either recepto r but not of control cells. These results are consistent with the ability o f each receptor to mediate entry of viruses expressing wild-type or Rid1 go and with results obtained previously with HVEM (HveA), a third HSV-I entry receptor. Undersulfation of GAGs in receptor-expressing cell lines predict ably reduced susceptibility to HSV-I infection. In contrast, susceptibility to cell fusion mediated by HVEM or nectin-1 was not reduced. Undersulfatio n of GAGs partially inhibited cell fusion mediated by nectin-2. We conclude that HSV-l-induced cell fusion requires a go-binding entry receptor, that ability of an HSV-1 strain to use HVEM, nectin-2 or nectin-1 for cell fusio n depends on the allele of go expressed and that GAGs may influence cell fu sion, dependent on the go-binding receptor used, but are less important for cell fusion mediated by HVEM, nectin-2 or nectin-1 than for viral entry. ( C) 2001 Elsevier Science B.V. All rights reserved.