title: HSV-1 infection through inhibitory receptor, PILRalpha.
abstract: Paired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of immune response. Several viruses that persistently infect hosts possess genes that encode ligands for inhibitory receptors in order to escape from host immune system. Herpes simplex virus type 1 (HSV-1) is one of the viruses that cause persistent infection. Here, we found that HSV-1-infected cells express a ligand for paired immunoglobulin like-type 2 receptor (PILR)alpha, one of paired inhibitory receptors mainly expressed on myeloid cells such as monocytes, macrophages and dendritic cells. Furthermore, we have identified that glycoprotein B (gB), an envelope protein of HSV-1, is a ligand for PILRalpha by mass spectrometry analysis. Because gB is essential for HSV-1 to infect cells, we analyzed function of PILRalpha in HSV-1 infection. When PILRalpha was transfected into CHO-K1 cells, which is resistant to HSV-1 infection, the PILRalpha-transfected CHO-K1 cells became permissive to HSV-1 infection. We further addressed weather PILRalpha is involved in the HSV-1 infection of primary human cells. CD14-positive monocytes that express both PILRalpha and HVEM, a glycoprotein D receptor, were susceptible to HSV-1 infection. In contrast, HSV-1 did not infect CD14-negative lymphocytes that express HVEM but not PILRalpha. Furthermore, HSV-1 infection of monocyte was blocked by both anti-PILRalpha mAb and anti-HVEM antiserum. These findings indicated that both gB and gD receptors play an important role in HSV-1 infection. We have shown, for the first time, that viruses use an inhibitory immune receptor to enter a cell. Invasion into hematopoietic cells by using inhibitory receptors should be beneficial to the virus because binding to inhibitory receptors may not only provide entry, but also trigger the inhibitory receptor to suppress the immune functions of the infected cell.
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Satoh
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D006561:Herpes Simplex / Q000209:etiology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000821:virology; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000502:physiology; D014759:Viral Envelope Proteins / Q000378:metabolism / Q000502:physiology
chemical_list: D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; C412263:PILRA protein, human; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus