The murine nectin1α (mNectin1α), a homolog of human nectin1α (hNectin1α, or PRR1, HveC), mediates the entry of herpes simplex virus (HSV) into cells. Previously, we reported that the binding of hNectin1 to HSV glycoprotein D (gD) was readily detectable, whereas the binding of mNectin1 to gD was not detectable, thus raising the question whether mNectin1 mediates a gD-dependent or a gD-independent pathway of entry. Here we report comparative binding studies of murine- and human-nectin1α to virions and to gD. The assays consistently showed either a very weak binding or no detectable binding of murine nectin1α to gD. They included (i) binding of soluble mNectin1-Fc or hNectin1-Fc to virions and competition of the binding by soluble gD(Δ290-299t) and by monoclonal antibodies to gD; (ii) pull-down experiments of wt gD from lysates of infected cells; and (iii) ELISA binding of soluble gD(Δ290-299t) to cells expressing mNectin1 or hNectin1. In contrast to the binding studies, the entry studies readily showed that entry mediated by mNectin1 was dependent on gD. Thus, a gDnull (gD-/-) mutant virus was unable to enter mNectin1-expressing cells, and entry of wild-type virus was inhibited by antibodies to gD or soluble gD at similar concentrations. We infer that gD represents a weak ligand in the interaction between mNectin1 and virions, whereas it represents a strong and the major ligand for hNectin1. Yet gD is required in HSV-1 entry mediated by mNectin1α. We conclude that a high-affinity binding of the receptor to gD is not a requirement in the gD-dependent pathway of HSV entry to cells. © 2001 Academic Press.

Comparison of murine and human nectin1 binding to herpes simplex virus glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD-dependent pathway of entry / Menotti L.; Avitabile E.; Dubreuil P.; Lopez M.; Campadelli-Fiume G.. - In: VIROLOGY. - ISSN 0042-6822. - ELETTRONICO. - 282:2(2001), pp. 256-266. [10.1006/viro.2001.0850]

Comparison of murine and human nectin1 binding to herpes simplex virus glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD-dependent pathway of entry

Menotti L.;Avitabile E.;Campadelli-Fiume G.
2001

Abstract

The murine nectin1α (mNectin1α), a homolog of human nectin1α (hNectin1α, or PRR1, HveC), mediates the entry of herpes simplex virus (HSV) into cells. Previously, we reported that the binding of hNectin1 to HSV glycoprotein D (gD) was readily detectable, whereas the binding of mNectin1 to gD was not detectable, thus raising the question whether mNectin1 mediates a gD-dependent or a gD-independent pathway of entry. Here we report comparative binding studies of murine- and human-nectin1α to virions and to gD. The assays consistently showed either a very weak binding or no detectable binding of murine nectin1α to gD. They included (i) binding of soluble mNectin1-Fc or hNectin1-Fc to virions and competition of the binding by soluble gD(Δ290-299t) and by monoclonal antibodies to gD; (ii) pull-down experiments of wt gD from lysates of infected cells; and (iii) ELISA binding of soluble gD(Δ290-299t) to cells expressing mNectin1 or hNectin1. In contrast to the binding studies, the entry studies readily showed that entry mediated by mNectin1 was dependent on gD. Thus, a gDnull (gD-/-) mutant virus was unable to enter mNectin1-expressing cells, and entry of wild-type virus was inhibited by antibodies to gD or soluble gD at similar concentrations. We infer that gD represents a weak ligand in the interaction between mNectin1 and virions, whereas it represents a strong and the major ligand for hNectin1. Yet gD is required in HSV-1 entry mediated by mNectin1α. We conclude that a high-affinity binding of the receptor to gD is not a requirement in the gD-dependent pathway of HSV entry to cells. © 2001 Academic Press.
2001
Comparison of murine and human nectin1 binding to herpes simplex virus glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD-dependent pathway of entry / Menotti L.; Avitabile E.; Dubreuil P.; Lopez M.; Campadelli-Fiume G.. - In: VIROLOGY. - ISSN 0042-6822. - ELETTRONICO. - 282:2(2001), pp. 256-266. [10.1006/viro.2001.0850]
Menotti L.; Avitabile E.; Dubreuil P.; Lopez M.; Campadelli-Fiume G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/872857
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