Nectin2 alpha (PRR2 alpha or HveB) and nectin2 delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D

The receptors for entry of herpes simplex viruses 1 and 2 (HSV-1 and -2), w idely expressed in human cell lines, are members of a subset of the immunog lobulin superfamily exemplified by herpesvirus entry mediator C (HveC) and the herpesvirus immunoglobulin-like receptor (HIgR). This report focuses on two members of this subset, herpesvirus entry mediator B (HveB), recently designated nectin2/PRR2 alpha, and its splice variant isoform, nectin2/PRR2 delta\. Nectin2 alpha and -delta share the ectodomain but differ in the tr ansmembrane and cytoplasmic regions. HveB was reported to enable entry of H SV-1 carrying mutations in glycoprotein D (gD) and of HSV-2, but not of wil d-type (wt) HSV-1. We report that (i) both nectin2 alpha and -delta served as receptors for the entry of HSV-1 mutant viruses HSV-1(U10) and -(U21) an d AP7(r) that carry the Leu25Pro substitution in gD but not for HSV-1 mutan ts U30 and R5000 that carry the Ser140 or Ala185 substitution in gD. All of these mutants were able to overcome the block to entry mediated by express ion of wt gD. (ii) Infection of cells expressing nectin2 alpha or -delta re quired exposure to multiplicities of infection about 100-fold higher than t hose required to infect cells expressing HveC or HIgR. (iii) go from HSV-1( U21) bound in vitro soluble forms of nectin2. The association was weaker th an that to the soluble form of HveC/HIgR. Binding of wt HSV-1 go to soluble nectin2 was not detectable. (iv) A major region of nectin2 functional in v irus entry mapped to the V domain, located at the N terminus.