The novel receptors that mediate the entry of herpes simplex viruses and animal alphaherpesviruses into cells

An extended array of cell surface molecules serve as receptors for HSV entr y into cells. In addition to the heparan sulphate glycosaminoglycans, which mediate the attachment of virion to cells, HSV requires an entry receptor. The repertoire of entry receptors into human cells includes molecules from three structurally unrelated molecular families. They are (i) HveA (herpes virus entry mediator A), (ii) members of the nectin family, (iii) 3-O-sulph ated heparan sulphate. The molecules have different attributes and play pot entially different roles in HSV infection and spread to human tissues. All the human entry receptors interact physically with the virion envelope glyc oprotein D (gD). (i) HveA is a member of the TNF-receptor family. It mediat es entry of a restricted range of HSV strains. Its expression is restricted to few lineages (e.g. T-lymphocytes). (ii) The human nectin1 alpha (HIgR), nectin1 delta (PRR1-HVeC), and the nectin2 alpha (PRR2 alpha-HveB) and nec tin2 delta (PRR2 delta) belong to the immunoglobulin superfamily. They are homologues of the poliovirus receptor (CD155), with which they share the ov erall structure of the ectodomain. The human nectin1 alpha-delta are broadl y expressed in cell lines of different lineages, are expressed in human tis sue targets of HSV infection, serve as receptors for all HSV-1 and HSV-2 st rains tested and mediate entry not only of free virions, but also cell-to-c ell spread of virus. (iii) The 3-O-sulphated heparan sulphate is expressed in some selected human cell lines (e.g, endothelial and mast cells) and hum an tissues, and mediates entry of HSV-1, but not HSV-2. The human nectin2 a lpha and nectin2 delta serve as receptors for a narrow range of viruses. A characteristic of the human nectin1 alpha-delta is the promiscuous species non-specific receptor activity towards the animal alphaherpesviruses, pseud orabies virus (PrV) and bovine herpesvirus 1 (BHV-1). By contrast with the human nectin1 delta, its murine homologue (mNectin1 delta) does not bind gD at detectable level, yet it mediates entry of HSV, as well as of PrV and B HV-1. This provides the first example of a mediator of HSV entry independen t of a detectable interaction with gD. Copyright (C) 2000 John Wiley & Sons , Ltd.