title: The murine homolog of human Nectin1delta serves as a species nonspecific mediator for entry of human and animal alpha herpesviruses in a pathway independent of a detectable binding to gD.
abstract: The full-length cDNA of the murine homolog of human nectin1delta (mNectin1delta), 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. mNectin1delta 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 mNectin1delta and human nectin1delta (hNectin1delta)-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 mNectin1delta in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1delta failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1delta and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1delta fails to be sequestered by HSV gD. We conclude that mNectin1delta serves as a species-nonspecific mediator for entry of the human and animal alphaherpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD.
authors.affiliation: Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, Via San Giacomo, 12, 40126 Bologna, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Menotti
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: E
authors.initials: E
authors.lastname: Avitabile
authors.forename: A
authors.initials: A
authors.lastname: Stefan
authors.forename: F
authors.initials: F
authors.lastname: Cocchi
authors.forename: J
authors.initials: J
authors.lastname: Adelaide
authors.forename: E
authors.initials: E
authors.lastname: Lecocq
authors.forename: P
authors.initials: P
authors.lastname: Dubreuil
authors.forename: G
authors.initials: G
authors.lastname: Campadelli-Fiume
mesh_terms: D016475:3T3 Cells; D018138:Alphaherpesvirinae / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006224:Cricetinae; D018076:DNA, Complementary; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D000075983:Nectins; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D018139:Simplexvirus / Q000502:physiology*; D013552:Swine; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D007072:Immunoglobulin D; D008565:Membrane Proteins; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D011991:Receptors, Virus; C066100:poliovirus receptor