The murine homolog of human Nectin1 delta serves as a species nonspecific mediator for entry of human and animal alpha herpesviruses in a pathway independent of a detectable binding to gD

The full-length cDNA of the murine homolog of human nectin1 delta (mNectin1 delta), also known as human poliovirus receptor related 1 (PRR1) or herpes virus entry mediator C. was cloned and showed a >90% identity with its huma n counterpart. mNectin1 delta is expressed in some murine cell lines, exemp lified by NIH 3T3 and L cells, and in murine tissues. It mediates entry of an extended range of herpes simplex virus (HSV) strains, porcine pseudorabi es virus (PrV), and bovine herpesvirus 1. A soluble form of the mediator bl ocked infectivity in mNectin1 delta and human nectin1 delta (hNectin1 delta )-expressing cells, suggesting a physical interaction of the mediator with virions. The higher concentrations of soluble mNectin1 required to block in fectivity relative to soluble hNectin1 suggest that the target of the two m olecules is not identical. Entry of HSV, but not PrV. was blocked by solubl e mNectin1 delta in NIH 3T3 and L cells. Two features were unexpected. Firs t, soluble mNectin1 delta failed to physically interact with HSV glycoprote in D (gD) at a detectable level, although it interacted physically with vir ions. Second, coexpression of mNectin1 delta and HSV gD did not restrict HS V or PrV infection, whereas coexpression of hNectin and go did restrict inf ection, suggesting that mNectin1 delta fails to be sequestered by Hsv gD. W e conclude that mNectin1 delta serves as a species-nonspecific mediator for entry of the human and animal alpha herpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD.