The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D

Cocchi, Francesca; Lopez, Marc; Menotti, Laura; Aoubala, Mustapha; Dubreuil, Patrice; Campadelli-Fiume, Gabriella

doi:10.1073/pnas.95.26.15700

Cited by 115 publications

(154 citation statements)

References 36 publications

(23 reference statements)

Supporting

Mentioning

144

Contrasting

Order By: Relevance

“…Antibodies-The mAbs R1.302, CK6, and CK8 directed to the V domain of hNectin1 were described previously (25,27). The anti-PVR antibody PV.404 was described previously (28).…”

Section: Methodsmentioning

confidence: 99%

“…To further characterize nectin3 and nectin4 binding regions on nectin1, we carried out blocking experiments with a panel of antinectin1 mAbs (R1.302, CK6, and CK8) whose epitopes were previously mapped to the V domain (25,27). First we further refined the nectin1 region recognized by these mAbs.…”

Section: Nectin1 V Domain Regions Involved In Nectin3 and Nectin4mentioning

confidence: 99%

“…The distal V domain of nectin1 plays a central role not only in homophilic and heterophilic trans-interactions but also in the interaction with the envelope glycoprotein D (gD) of HSV, pseudorabies virus, and bovine herpes virus-1 (25,26). Recent studies based on monoclonal antibody (mAb) competition or chimeric nectin1/PVR molecules identified the C-CЈ-CЉ ␤-strands and intervening loops of the nectin1 V domain as the gD binding site.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Fabre¹,

Reymond²,

Cocchi³

et al. 2002

Journal of Biological Chemistry

Self Cite

113

View full text Add to dashboard Cite

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.

show abstract

“…Antibodies-The mAbs R1.302, CK6, and CK8 directed to the V domain of hNectin1 were described previously (25,27). The anti-PVR antibody PV.404 was described previously (28).…”

Section: Methodsmentioning

confidence: 99%

Section: Nectin1 V Domain Regions Involved In Nectin3 and Nectin4mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Fabre¹,

Reymond²,

Cocchi³

et al. 2002

Journal of Biological Chemistry

Self Cite

113

View full text Add to dashboard Cite

show abstract

“…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)(13)(14)(15). Critical residues were located in the 69-75 region and at positions 77 and 85 (16,17).…”

mentioning

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.

Self Cite

132

157

View full text Add to dashboard Cite

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...

show abstract

“…Interaction between gD and cell receptors allows virion entry into cells to be infected (22)(23)(24)(25). At least one of the cell receptors for gD, namely herpesvirus entry mediator A (HveA; also known as HVEM, TNFRSF14), belongs to the family of tumor necrosis factor receptors, which play a central role in mediating signal transduction leading to death receptor-associated apoptosis (26 -28).…”

mentioning

confidence: 99%

Protection by Herpes Simplex Virus Glycoprotein D against Fas-mediated Apoptosis

Medici

Sciortino

Perri

et al. 2003

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

Signals involved in protection against apoptosis by herpes simplex virus 1 (HSV-1) were investigated. Using U937 monocytoid cells as an experimental model, we have demonstrated that HSV-1 rendered these cells resistant to Fas-induced apoptosis promptly after infection. UV-inactivated virus as well as the envelope glycoprotein D (gD) of HSV-1, by itself, exerted a protective effect on Fas-induced apoptosis. NF-B was activated by gD, and protection against Fas-mediated apoptosis by gD was abolished in cells stably transfected with a dominant negative mutant I-B␣, indicating that NF-B activation plays a role in the antiapoptotic activity of gD in our experimental model. Moreover, NF-B-dependent protection against Fas-mediated apoptosis was associated with decreased levels of caspase-8 activity and with the up-regulation of intracellular antiapoptotic proteins.Interest in the understanding of mechanisms by which viruses belonging to a variety of families regulate cell apoptosis has grown rapidly in recent years (1-3). Herpesviruses, due to the relatively large quantity of information contained in their genomes, seem particularly well equipped to exert a fine control over cell apoptosis (4). This occurs through various interactions among viral and cell products acting at different levels (5).Among herpesviruses, herpes simplex viruses have been shown to regulate apoptosis of infected cells both positively and negatively, according to the presence or absence of specific genes, experimental conditions, or specificity of target cells (6 -21).Glycoprotein D (gD) 1 is a main component of the external structure of HSV-1, and its function is essential for HSV-1 spread. Interaction between gD and cell receptors allows virion entry into cells to be infected (22)(23)(24)(25). At least one of the cell receptors for gD, namely herpesvirus entry mediator A (HveA; also known as HVEM, TNFRSF14), belongs to the family of tumor necrosis factor receptors, which play a central role in mediating signal transduction leading to death receptor-associated apoptosis (26 -28). Recent results have shown that gD delivered in trans blocks the apoptotic cascade triggered by HSV-1 mutants lacking the gene encoding gD in SK-N-SH cells (29,30). Cellular signals involved in the antiapoptotic action exerted by HSV-1-gD remain to be elucidated. Interestingly, overexpression of the gD receptor HveA has been shown to cause activation of the transcription factor, NF-B (28). Furthermore, it has been reported that engagement with HveA receptor of its natural ligand, LIGHT, can stimulate the activation of NF-B in different cellular systems (31,32). This suggests the possibility that also engagement of gD with HveA could lead to NF-B activation. The transcription factor NF-B consists of a homodimeric or heterodimeric complex of two subunits belonging to the highly conserved family of Rel-related proteins (33). The most important complex is that formed by two proteins with molecular masses of 50 kDa (p50) and 65 kDa (p65), respectively. This heterodimer is pre...

show abstract

The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D

Cited by 115 publications

References 36 publications

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

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

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

Protection by Herpes Simplex Virus Glycoprotein D against Fas-mediated Apoptosis

Contact Info

Product

Resources

About