The full-length cDNA of the murine homolog of human nectin1␦ (mNectin1␦), 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. mNectin1␦ 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 (PrV), and bovine herpesvirus 1. A soluble form of the mediator blocked infectivity in mNectin1␦ and human nectin1␦ (hNectin1␦)-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 mNectin1␦ in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1␦ failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1␦ and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1␦ fails to be sequestered by HSV gD. We conclude that mNectin1␦ serves as a species-nonspecific mediator for entry of the human and animal ␣herpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD. H erpes simplex virus (HSV) has a broad host range and can infect animals and cultured cells from species other than the natural host. Mouse is the commonly used small animal model in HSV research, including studies on latency, prototypic vaccines, antiviral compounds, and HSV-based vectors. The mouse can be infected by inoculation at peripheral sites, e.g., skin, vagina, or directly into the central nervous system. Infection mimics the infection in humans. Thus, following peripheral inoculation, the virus spreads to nerve endings of the sensory neurons, is transported in anterograde direction to the nuclei of sensitive neurons, where it establishes latency. Virus can be reactivated by exogenous stimuli, and after replication, moves in retrograde direction to peripheral tissues, where it induces lesions. This pattern of infection underscores the existence in mice of receptors for HSV entry into cells, and cell-to-cell spread, with pathways of transmission to tissues analogous to those in humans. Similar to HSV, the porcine ␣herpesvirus pseudorabies virus (PrV) has a very broad host range in cultured cells, and can infect and cause disease in animal species other than the natural host. Mice have been used for experimental infections and to trace the pattern of virus spread to the nervous system. In contrast, the host range of bovine herpesvirus 1 (BHV-1) appears to be narrower, probably reflecting limited availability also of cellular functions involved in postentry steps. A key question in the validation of the mouse animal model is to what exte...
