The murine homolog of human Nectin1δ serves as a species nonspecific mediator for entry of human and animal αherpesviruses in a pathway independent of a detectable binding to gD

Menotti, Laura; Lopez, Marc; Avitabile, Elisa; Stefan, Alessandra; Cocchi, Francesca; Adélaı̈de, José; Lecocq, Eric; Dubreuil, Patrice; Campadelli-Fiume, Gabriella

doi:10.1073/pnas.97.9.4867

Cited by 59 publications

(68 citation statements)

References 33 publications

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“…While this paper was being written, a report was published on a different allelic form of murine nectin-1␣ obtained from the C3H strain of mice (25). The isoform of nectin-1 described by these authors was the same as that described here, although it was designated nectin-1␦ for unexplained reasons.…”

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confidence: 74%

Striking Similarity of Murine Nectin-1α to Human Nectin-1α (HveC) in Sequence and Activity as a Glycoprotein D Receptor for Alphaherpesvirus Entry

Shukla¹,

Canto

Rowe³

et al. 2000

J Virol

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Members of the alphaherpesvirus subfamily exemplified by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), bovine herpesvirus 1 (BHV-1) and porcine pseudorabies virus (PRV) have a broad host range in cultured cells. They can also infect animal species other than the natural host and cause symptoms similar to those observed in their natural hosts. For these and other reasons, the mouse has been extensively used as an animal model to study various aspects of alphaherpesvirus pathogenesis including pathology, immune responses, latency, and transneuronal spread of infection. Consequently, there is considerable interest in defining the cell receptors for entry of HSV and other alphaherpesviruses into mouse cells as well as into cells of the natural hosts. The studies described here are part of a larger effort to determine whether evolutionarily related or distinct receptors are used by HSV for entry into mouse and human cells. If related receptors are used and these related receptors have similar expression patterns and functions in mice and humans, this strengthens the case for using mouse models of disease to dissect aspects of pathogenesis that depend on the susceptibility of cells to viral entry.Human and animal representatives of the alphaherpesvirus subfamily exhibit common requirements for entry into cells (26,34). The initial interaction of virus with cells involves binding of the virion glycoprotein gC, and in some cases gB, to cell surface glycosaminoglycans, preferentially heparan sulfate. Four envelope glycoproteins, gB, gD, gH, and gL, are required to mediate the fusion between the virion envelope and cell membrane that allows viral penetration. It is believed that interaction between gD and one of its cognate cell surface receptors triggers the process of fusion.Recently four human cell surface proteins have been identified as gD receptors that mediate the entry into cells of one or more of the alphaherpesviruses (13,29,37). One of these proteins is a newly described member of the tumor necrosis factor receptor family, originally designated the herpesvirus entry mediator (HVEM) (29), later designated herpesvirus entry protein A (HveA) (13, 37), and officially named TN-FRSF14. The other three proteins are related members of the immunoglobulin (Ig) superfamily, a subfamily including the poliovirus receptor (CD155) (24) and two proteins that are not receptors for poliovirus but were originally designated poliovirus receptor-related protein 1 (Prr1) (22) and poliovirus receptor-related protein 2 (Prr2) (10). CD155 mediates the entry of PRV and BHV-1 but has no activity for HSV strains (13). Prr2 was identified as an entry receptor for strains of HSV-1 that could not use HVEM for entry, was also found to be an entry receptor for HSV-2 and PRV, and was designated HveB (37). Prr1 was found to serve as an entry receptor for HSV-1, HSV-2, PRV, and BHV-1 and was designated HveC (13). Recently both HveB and HveC were shown to be homophilic cell adhesion molecules that localize to sites of cadherin-based cell j...

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confidence: 74%

Striking Similarity of Murine Nectin-1α to Human Nectin-1α (HveC) in Sequence and Activity as a Glycoprotein D Receptor for Alphaherpesvirus Entry

Shukla¹,

Canto

Rowe³

et al. 2000

J Virol

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“…pEA99 carries the HSV-1 gD gene in pcDNA3.1(Ϫ) (28). pEA101 carries the HSV-1 UL26.5 promoter in place of CMV promoter.…”

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confidence: 99%

The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry

Cocchi

Fusco

Menotti

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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132

157

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Entry of herpes simplex virus (HSV) 1 into cells requires the interaction of HSV gD with herpesvirus entry mediator or nectin1receptors, and fusion with cell membrane mediated by the fusion glycoproteins gB, gH, and gL. We report that the gD ectodomain in soluble form (amino acids 1-305) was sufficient to rescue the infectivity of a gD-null HSV mutant, indicating that gD does not need to be anchored to the virion envelope to mediate entry. Entry mediated by soluble gD required, in addition to the receptorbinding sites contained within residues 1-250, a discrete downstream portion (amino acids 261-305), located proximal to the transmembrane segment in full-length gD. We named it as profusion domain. The pro-fusion domain was required for entry mediated by virion-bound gD, because its substitution with the corresponding region of CD8 failed to complement the infectivity of gD ؊/؉ HSV. Furthermore, a receptor-negative gD (gD⌬6-259) inhibited virus infectivity when coexpressed with wild-type gD; i.e., it acted as a dominant-negative gD mutant. The pro-fusion domain is proline-rich, which is characteristic of regions involved in protein-protein interactions. P291L-P292A substitutions diminished the gD capacity to complement gD ؊/؉ HSV infectivity. We propose that gD forms a tripartite complex with its receptor and, by way of the proline-rich pro-fusion domain, with the fusion glycoproteins, or with one of them. The tripartite complex would serve to recruit͞activate the fusion glycoproteins and bring them from a fusion-inactive to a fusion-active state, such that they execute fusion of the virion envelope with cell membrane. H erpes simplex virus (HSV) enters cells through the coordinated action of four essential glycoproteins; gD, gB, gH, and gL, that act after the binding of gC and gB to the glycosaminoglycans of cell-surface proteoglycans (1, 2). Of the four glycoproteins required for entry, gD is the receptor-binding glycoprotein. It interacts with two alternative protein receptors, HVEM (herpesvirus entry mediator) and nectin1, that belong to the tumor necrosis factor receptor family (3), and to a growing family of intercellular adhesion molecules with Ig structure, respectively (4-8). The four essential glycoproteins required for HSV entry are required and are also sufficient to induce fusion of cells that express a gD receptor (9). The gD-binding site on HVEM maps mainly to the N-terminal cysteine-rich domain 1, with a hot spot at Y23 (10, 11). For nectin1, the N-terminal V domain, in particular its CCЈCЉ ridge (amino acids 64-104) is sufficient to mediate HSV entry (12-15). Critical residues were located in the 69-75 region and at positions 77 and 85 (16, 17). Insertion and deletion mutants in gD were the first mutants used to define functional regions (18). Subsequently, the x-ray crystal structure of the first 259 residues of gD [of the 315 that compose the ectodomain] was solved (19). The gD ectodomain is composed of an Ig-folded core (residues 56-184), with N-and C-terminal extensions. The latter folds bac...

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“…Recently a new family of adhesion molecules, which belongs to the immunoglobulin superfamily and is related to the poliovirus receptor (PVR), 1 has emerged and has been named nectin/PRR (poliovirus receptor-related). This family comprises at least five different members identified both in humans and rodents: nectin/PRR1, -2, -3, -4, and PVR (1)(2)(3)(4)(5)(6)(7)(8)(9)(10).…”

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confidence: 99%

Prominent Role of the Ig-like V Domain intrans-Interactions of Nectins

Fabre¹,

Reymond²,

Cocchi³

et al. 2002

Journal of Biological Chemistry

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114

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2؉ -independent homophilic and heterophilic processes through ectodomain trans-interactions. We have described a nectin trans-hetero-interaction network: nectin3 binds to nectin1, nectin2, and PVR; nectin1 also binds to nectin4. In the present study we compared the affinities of the different trans-interactions mediated by nectin1. We found that the K D of nectin1/nectin3 and nectin1/nectin4 interactions is 1 and 100 nM, respectively, whereas the K D of the nectin1-mediated homophilic interaction is 1 M. We show that nectin1/nectin3 and nectin1/nectin4 transhetero-interactions were mediated through trans V to V domain interactions, whereas C domains contributed to increase the affinity of the interaction. Nectin3 and nectin4 share a common binding region in the nectin1 V domain: (i) nectin3 strongly competed with nectin4 binding, (ii) nectin3 and nectin4 binding to nectin1 was reduced by a number of monoclonal antibodies directed against the nectin1 V domain, and (iii) the glycoprotein D of herpes simplex virus-1 that binds to the V domain of nectin1 reduced nectin3 and nectin4 binding. Finally, using chimeric nectin1/PVR receptors where PVR V domain ␤-strands were substituted with the corresponding regions of nectin1, the nectin3 and nectin4 minimal binding region on nectin1 V domain was mapped to the C-C-C؆-D ␤-strands.

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The murine homolog of human Nectin1δ serves as a species nonspecific mediator for entry of human and animal αherpesviruses in a pathway independent of a detectable binding to gD

Cited by 59 publications

References 33 publications

Striking Similarity of Murine Nectin-1α to Human Nectin-1α (HveC) in Sequence and Activity as a Glycoprotein D Receptor for Alphaherpesvirus Entry

Striking Similarity of Murine Nectin-1α to Human Nectin-1α (HveC) in Sequence and Activity as a Glycoprotein D Receptor for Alphaherpesvirus Entry

The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry

Prominent Role of the Ig-like V Domain intrans-Interactions of Nectins

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