A cell surface protein with herpesvirus entry activity (Hveb) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus

Morgyn S. Warner, Robert J. Geraghty, Wanda M. Martinez, Rebecca I. Montgomery, J. Charles Whitbeck, Ruliang Xu, Roselyn J. Eisenberg, Gary H. Cohen, Patricia G. Spear

Research output: Contribution to journalArticle

382 Scopus citations

Abstract

Certain mutant strains of herpes simplex virus type 1 (HSV-1) are unable to infect cells in which entry is dependent on HVEM, the previously described herpesvirus entry mediator designated here as herpesvirus entry protein A (HveA). These mutant viruses can infect other cells where entry is apparently dependent on other co-receptors. The mutant virus HSV-1 (KOS)Rid1 was used to screen a human cDNA expression library for ability of transfected plasmids to convert resistant Chinese hamster ovary cells to susceptibility to virus entry. A plasmid expressing the previously described poliovirus receptor- related protein 2 (Prr2) was isolated on the basis of this activity. This protein, designated here as HveB, was shown to mediate the entry of three mutant HSV-1 strains that cannot use HVEM as co-receptor, but not wild-type HSV-1 strains. HveB also mediated the entry of HSV-2 and pseudorabies virus but not bovine herpesvirus type 1. HveB was expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes, and primary activated T lymphocytes. Antibodies specific for HveB blocked infection of HveB- expressing Clio cells and a human fibroblastic cell strain HEL299. Differences in ability of HSV-1 and HSV-2 strains to use HveB for entry should influence the types of cells that can be infected and thereby account in part for serotype and strain differences in tissue tropism and pathogenicity.

Original languageEnglish (US)
Pages (from-to)179-189
Number of pages11
JournalVirology
Volume246
Issue number1
DOIs
StatePublished - Jun 20 1998
Externally publishedYes

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