Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D.
The receptors for entry of herpes simplex viruses 1 and 2 (HSV-1 and -2), widely expressed in human cell lines, are members of a subset of the immunoglobulin superfamily exemplified by herpesvirus entry mediator C (HveC) and the herpesvirus immunoglobulin-like receptor (HIgR). This report focuses on two members of this subset, herpesvirus entry mediator B (HveB), recently designated nectin2/PRR2alpha, and its splice variant isoform, nectin2/PRR2delta. Nectin2alpha and -delta share the ectodomain but differ in the transmembrane and cytoplasmic regions. HveB was reported to enable entry of HSV-1 carrying mutations in glycoprotein D (gD) and of HSV-2, but not of wild-type (wt) HSV-1. We report that (i) both nectin2alpha and -delta served as receptors for the entry of HSV-1 mutant viruses HSV-1(U10) and -(U21) and AP7(r) that carry the Leu25Pro substitution in gD but not for HSV-1 mutants U30 and R5000 that carry the Ser140 or Ala185 substitution in gD. All of these mutants were able to overcome the block to entry mediated by expression of wt gD. (ii) Infection of cells expressing nectin2alpha or -delta required exposure to multiplicities of infection about 100-fold higher than those required to infect cells expressing HveC or HIgR. (iii) gD from HSV-1(U21) bound in vitro soluble forms of nectin2. The association was weaker than that to the soluble form of HveC/HIgR. Binding of wt HSV-1 gD to soluble nectin2 was not detectable. (iv) A major region of nectin2 functional in virus entry mapped to the V domain, located at the N terminus.
Lopez
M
M
Institute of Cancerology and Immunology, INSERM U119, Marseille, France.
Cocchi
F
F
Menotti
L
L
Avitabile
E
E
Dubreuil
P
P
Campadelli-Fiume
G
G
D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007930:Leucine; D009154:Mutation; D000075983:Nectins; D011392:Proline; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D020033:Protein Isoforms; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D011392:Proline; D007930:Leucine