PILRα Is a Herpes Simplex Virus-1 Entry Coreceptor That Associates with Glycoprotein B

Abstract

Glycoprotein B (gB) is one of the essential components for infection by herpes simplex virus-1 (HSV-1). Although several cellular receptors that associate with glycoprotein D (gD), such as herpes virus entry mediator (HVEM) and Nectin-1, have been identified, specific molecules that mediate HSV-1 infection by associating with gB have not been elucidated. Here, we found that paired immunoglobulin-like type 2 receptor (PILR) alpha associates with gB, and cells transduced with PILRalpha become susceptible to HSV-1 infection. Furthermore, HSV-1 infection of human primary cells expressing both HVEM and PILRalpha was blocked by either anti-PILRalpha or anti-HVEM antibody. Our results demonstrate that cellular receptors for both gB and gD are required for HSV-1 infection and that PILRalpha plays an important role in HSV-1 infection as a coreceptor that associates with gB. These findings uncover a crucial aspect of the mechanism underlying HSV-1 infection.

Herpes Simplex Virus gD Forms Distinct Complexes with Fusion Executors gB and gH/gL in Part through the C-terminal Profusion Domain

“…With respect to gB, the crystal structure shows a trimer with a central coiled-coil and an overall structure similar to that of the fusion glycoprotein G of vesicular stomatitis virus in its postfusion conformation (21,22). Recently, a receptor for gB was described (23). Of note, although for virus-to-cell entry and for cell-cell fusion, fusion requires the simultaneous presence of gB and gH/gL, fusion of perinuclear virions with the outer nuclear membranes appears to necessitate either gH/gL or gB (24).…”

Pattern recognition receptors in microbial keratitis

“…[129][130][131] Several host surface receptors have been identified, including herpes virus entry mediator, nectin-1, 3-O-sulphated heparan sulphate and paired immunoglobulin-like type 2 receptor α (PILR-α). [132][133][134][135] However, a study by Shukla et al 136 identified nectin-1 as being the crucial mediator in a murine model of corneal infection. Of note when considering the mechanism of HSV1 infection is the fact that phylogenetic analysis suggests the evolution of at least six distinct HSV1 genogroups, with multiple recombination events detected in the genome coding for glycoproteins.…”

Role of Membrane Rafts in Viral Infection

“…HSV belonging to the family of alpha-herpes viruses, typical pathogens responsible for mucosal lesions of the mouth and genital organs in humans, binds and enters host cells by a complex process involving the essential viral glycoproteins B (gB), gD, gH, and gL and multiple cellular molecules including the tumor necrosis factor receptor (TNFR) family [123], nectin-1 or nectin-2 (two members of the immunoglobulin superfamily) [124], paired immunoglobulin-like type 2 receptor (PILR) [125], and particular type of modified HSPGs [126,127]. Raft associations of TNFR are essential for TNFalpha-mediated NF-B activation [128].…”