Cell-to-cell spread of wild-type herpes simplex virus type 1, but not of syncytial strains, is mediated by the immunoglobulin-like receptors that mediate virion entry, Nectin1 (PRR1/HveC/HIgR) and Nectin2 (PRR2/HveB)

The immunoglobulin-like receptors that mediate entry of herpes simplex viru s type I (HSV-1) into human cells were found to mediate the direct cell-to- cell spread of wild-type virus. The receptors here designated Nedin1 alpha and -delta and Nectin2 alpha were originally designated HIgR, PRR1/HveC, an d PRR2 alpha/HveB, respectively. We report the following. (i) Wild-type HSV -1 spreads from cell to cell in J cells expressing nectin1 alpha or nectin1 delta but not in parental J cells that are devoid of entry receptors. A mo noclonal antibody to nectin1, which blocks entry, also blocked cell-to-cell spread in nectin1-expressing J cells. Moreover, wild-type virus did not sp read from a receptor positive to a receptor-negative cell. (ii) The antibod y to nectin1 blocked transmission of wild-type virus in a number of human c ell lines, with varying efficiencies, suggesting that nectin1 is the princi pal mediator of wild-type virus spread in a variety of human cell lines. (i ii) Nectin1 did not mediate cell fusion induced by the syncytial strains HS V-1(MP) and HFEM-syn, (iv) Nectin2 alpha could serve as a receptor for spre ad of a mutant virus carrying the L25P substitution in glycoprotein D, but not of wild-type virus, in agreement with its ability to mediate entry of t he mutant but not of wild-type virus.