Entry of Alphaherpesviruses Mediated by Poliovirus Receptor-Related Protein 1 and Poliovirus Receptor

TLDR

A human immunoglobulin superfamily member, poliovirus receptor‑related protein 1 (Prr1, here called HveC), mediates entry of several alphaherpesviruses such as HSV‑1, HSV‑2, PRV, and BHV‑1. Secreted HveC blocks HSV‑1 infection, indicating direct viral interaction, while poliovirus receptor mediates PRV and BHV‑1 entry but not HSV, and HveC’s expression in human epithelial and neuronal cells makes it the likely coreceptor enabling HSV‑1/2 mucosal entry and neural spread.

Abstract

A human member of the immunoglobulin superfamily was shown to mediate entry of several alphaherpesviruses, including herpes simplex viruses (HSV) 1 and 2, porcine pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). This membrane glycoprotein is poliovirus receptor-related protein 1 (Prr1), designated here as HveC. Incubation of HSV-1 with a secreted form of HveC inhibited subsequent infection of a variety of cell lines, suggesting that HveC interacts directly with the virus. Poliovirus receptor (Pvr) itself mediated entry of PRV and BHV-1 but not of the HSV strains tested. HveC was expressed in human cells of epithelial and neuronal origin; it is the prime candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect epithelial cells on mucosal surfaces and spread to cells of the nervous system.