title: Herpes B virus utilizes human nectin-1 but not HVEM or PILRα for cell-cell fusion and virus entry.
abstract: To investigate the requirements of herpesvirus entry and fusion, the four homologous glycoproteins necessary for herpes simplex virus (HSV) fusion were cloned from herpes B virus (BV) (or macacine herpesvirus 1, previously known as cercopithecine herpesvirus 1) and cercopithecine herpesvirus 2 (CeHV-2), both related simian simplexviruses belonging to the alphaherpesvirus subfamily. Western blots and cell-based enzyme-linked immunosorbent assay (ELISA) showed that glycoproteins gB, gD, and gH/gL were expressed in whole-cell lysates and on the cell surface. Cell-cell fusion assays indicated that nectin-1, an HSV-1 gD receptor, mediated fusion of cells expressing glycoproteins from both BV and CeHV-2. However, herpesvirus entry mediator (HVEM), another HSV-1 gD receptor, did not facilitate BV- and CeHV-2-induced cell-cell fusion. Paired immunoglobulin-like type 2 receptor alpha (PILRα), an HSV-1 gB fusion receptor, did not mediate fusion of cells expressing glycoproteins from either simian virus. Productive infection with BV was possible only with nectin-1-expressing cells, indicating that nectin-1 mediated entry while HVEM and PILRα did not function as entry receptors. These results indicate that these alphaherpesviruses have differing preferences for entry receptors. The usage of the HSV-1 gD receptor nectin-1 may explain interspecies transfer of the viruses, and altered receptor usage may result in altered virulence, tropism, or pathogenesis in the new host. A heterotypic cell fusion assay resulting in productive fusion may provide insight into interactions that occur to trigger fusion. These findings may be of therapeutic significance for control of deadly BV infections.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine of Northwestern University, Chicago, Illinois, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Fan
authors.forename: Melanie
authors.initials: M
authors.lastname: Amen
authors.forename: Mallory
authors.initials: M
authors.lastname: Harden
authors.forename: Alberto
authors.initials: A
authors.lastname: Severini
authors.forename: Anthony
authors.initials: A
authors.lastname: Griffiths
authors.forename: Richard
authors.initials: R
authors.lastname: Longnecker
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015870:Gene Expression; D006568:Herpesvirus 1, Cercopithecine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000075983:Nectins; D011971:Receptors, Immunologic / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; C000619010:NECTIN1 protein, human; D000075983:Nectins; C412263:PILRA protein, human; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; D014759:Viral Envelope Proteins