The murine homolog of human Nectin1δ serves as a species nonspecific mediator for entry of human and animal αherpesviruses in a pathway independent of a detectable binding to gD

The full-length cDNA of the murine homolog of human nectin1δ (mNectin1δ), also known as human poliovirus receptor related 1 (PRR1) or herpesvirus entry mediator C, was cloned and showed a >90% identity with its human counterpart, mNectin1δ is expressed in some murine cell lines, exemplified by NIH 3T3 and L cells, and in murine tissues. It mediates entry of an extended range of herpes simplex virus (HSV) strains, porcine pseudorabies virus (PRY), and bovine herpesvirus 1. A soluble form of the mediator blocked infectivity in mNectin1δ and human nectin1δ (hNectin1δ)- expressing cells, suggesting a physical interaction of the mediator with virions. The higher concentrations of soluble mNectin1 required to block infectivity relative to soluble hNectin1 suggest that the target of the two molecules is not identical. Entry of HSV, but not PrV, was blocked by soluble mNectin1δ in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1δ failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1δ and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1δ fails to be sequestered by HSV gD. We conclude that mNectin1δ serves as a species-nonspecific mediator for entry of the human and animal αherpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD.