Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion

Zhang, Na; Yan, Jinghua; Lu, Guangwen; Guo, Zhaoxin; Fan, Zheng; Wang, Jiawei; Shi, Yi; Qi, Jianxun; Gao, George F.

doi:10.1038/ncomms1571

Cited by 104 publications

(150 citation statements)

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“…HVEM belongs to the tumor necrosis factor family (6, 7), and nectin-1 is a cell adhesion molecule of the immunoglobulin superfamily (32). gD-receptor interactions have been revealed by using X-ray structural analyses (4,8,35). To test whether aptamer-1 has the ability to interfere with the gD-receptor (HVEM) interaction, we established an SPR-based competition assay (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Both HVEM and nectin-1 proteins were purchased from Sino Biological Inc. (Beijing, China). HVEM and nectin-1 were ex- (8,35). HSV-1 gD is shown in purple, its N-terminal residues (aa 1 to 37) are shown in blue, and the nectin-1 receptor is shown in green.…”

Section: Viral Proteinsmentioning

confidence: 99%

“…Recombinant HSV-1 gD prepared from Pichia pastoris, containing amino acids 1 to 319, was obtained from either Cortex Biochem or Vybion Inc. (New York, NY) or was expressed as a C-terminal His tag fusion protein (1 to 285 amino acids) in baculovirus, as described previously by Zhang et al (35). We purchased the purified HSV-2 gD protein from Vybion Inc. (New York, NY) (Fig.…”

Section: Viral Proteinsmentioning

confidence: 99%

“…Recently, the structure of gD bound to another receptor, nectin-1, was also determined by two groups ( Fig. 1c and d) (8,35). Those studies revealed that gD contains a V-like Ig fold between residues 56 and 184.…”

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confidence: 99%

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Aptamer That Binds to the gD Protein of Herpes Simplex Virus 1 and Efficiently Inhibits Viral Entry

Gopinath

Hayashi

Kumar

2012

J Virol

105

107

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The ectodomain of the gD protein of herpes simplex viruses (HSVs) plays an important role in viral entry by binding to specific cellular coreceptors and mediating viral entry to the host cells. In the present study, we isolated RNA aptamers (aptamer-1 and aptamer-5) that specifically bind to the gD protein of HSV-1 with high affinity and are able to discriminate the gD protein of a different virus, HSV-2. Aptamer-1 efficiently interfered with the interaction between the gD protein and the HSV-1 target cell receptor (HVEM) in a dose-dependent manner. The 50% effective concentration (EC 50 ) of aptamer-1 was estimated to be in the nanomolar range (60 nM). Furthermore, aptamer-1 was analyzed for anti-HSV-1 activity by using plaque assays, and it efficiently inhibited viral entry with an estimated K i of 0.8 M. To expand the future applications of aptamer-1, a shorter variant was designed by using both mapping and boundary analyses, resulting in the mini-1 aptamer (44-mer). Compared to the fulllength aptamer, mini-1 had at least as high an affinity, specificity, and ability to interfere with gD-HVEM interactions. These studies suggest that the mini-1 aptamer could be explored further as an anti-HSV-1 topical therapy designed to prevent the risk of acquiring HSV-1 infection through physical contact. Herpes simplex virus 1 (HSV-1) and HSV-2 are widespread human pathogens that infect primarily epithelial tissues before spreading to the nervous system, where they become latent. The genomes of HSV-1 and HSV-2 share 50 to 70% homology, and the two viruses also share several cross-reactive epitopes. The entry of HSV into the host cell begins with the binding of viral proteins gC and gB to proteoglycans on the host cell surface. This binding interaction is then followed by the coordinated action of four essential glycoproteins: gD, gB, gH, and gL (3, 30). Of these four glycoproteins, the gD protein is required for binding to the specific cellular receptors for viral entry. The gD protein recognizes two protein receptors, herpesvirus entry mediator (HVEM) (34) and nectin-1 (25). In addition to these receptor proteins, HSV-1 entry can also be mediated by 3-O-sulfated-modified heparan sulfate (29). The gD proteins of HSV-1 and HSV-2 are highly homologous proteins, with a sequence identity of around 86% within the ectodomain region (amino acids [aa] 1 to 319).The structures of the gD protein of HSV-1 have been solved, both in the absence (Fig. 1a) (4) and in the presence (Fig. 1b) (20) of its cognate receptor, HVEM. Recently, the structure of gD bound to another receptor, nectin-1, was also determined by two groups (Fig. 1c and d) (8, 35). Those studies revealed that gD contains a V-like Ig fold between residues 56 and 184. This structural feature is commonly found in cell surface adhesion molecules. N-and C-terminal extensions flank this fold and are unfolded and disordered in the absence of the gD receptor. However, in the HVEM-bound form, the N terminus of gD folds into a hairpin structure that binds to HVEM (4). This recept...

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Section: Resultsmentioning

confidence: 99%

Section: Viral Proteinsmentioning

confidence: 99%

Section: Viral Proteinsmentioning

confidence: 99%

mentioning

confidence: 99%

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Aptamer That Binds to the gD Protein of Herpes Simplex Virus 1 and Efficiently Inhibits Viral Entry

Gopinath

Hayashi

Kumar

2012

J Virol

105

107

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“…These proteins are expressed in commissural axons and floor plate cells, respectively, during the early development of the vertebrate central nervous system, and this heterophilic transinteraction is critically involved in the control of axonal guidance (12). In addition to cell-cell adhesion, the heterophilic interactions of nectins with a member of other protein families lead to different biological outcomes such as immune modulation and hostpathogen interactions (13)(14)(15).…”

mentioning

confidence: 99%

Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell–cell adhesion

Samanta¹,

Ramagopal

Rubinstein

et al. 2012

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

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Nectins are members of the Ig superfamily that mediate cell-cell adhesion through homophilic and heterophilic interactions. We have determined the crystal structure of the nectin-2 homodimer at 1.3 Å resolution. Structural analysis and complementary mutagenesis studies reveal the basis for recognition and selectivity among the nectin family members. Notably, the close proximity of charged residues at the dimer interface is a major determinant of the binding affinities associated with homophilic and heterophilic interactions within the nectin family. Our structural and biochemical data provide a mechanistic basis to explain stronger heterophilic versus weaker homophilic interactions among these family members and also offer insights into nectin-mediated transinteractions between engaging cells.nectin-2 dimer | cell adhesion molecule | immunoglobulin superfamily | X-ray crystallography

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Nanostructures/Graphene/Silicon Junction‐Based High‐Performance Photodetection Systems: Progress, Challenges, and Future Trends

Iqbal

Anwar

Malik

et al. 2023

Adv Materials Inter

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Graphene, due to its exceptional optoelectronic characteristics, high charge carrier mobility, wide absorption band, strong light‐matter interactions, and its adjustable nature, has attracted a lot of interest. In light of this, an attempt was made to successfully deposit graphene on a silicon substrate. This results in the formation of a Schottky junction, which could extend the operation window of the graphene/silicon hybrid device to the near‐infrared (NIR) region. Furthermore, since photodetectors built with Van der Waal heterostructures successfully extend the lifespan of dynamic charge carriers with improved the transportation range and speed of charge separation for effective photodetection, the technical development of optoelectronic devices has been greatly accelerated. Recent developments in graphene‐silicon junction‐based devices, their photodetection effectiveness, and active factors that can be used in a variety of applications are outlined, including optical synaptic systems, optical spectrometers, plasmonic devices, optical waveguides, and ultrafast photodetectors. Moreover, the shortcomings of the present optoelectronic devices are also concisely reviewed, along with the viable solutions offered by this new device and its application in next‐generation devices.

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Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion

Cited by 104 publications

References 57 publications

Aptamer That Binds to the gD Protein of Herpes Simplex Virus 1 and Efficiently Inhibits Viral Entry

Aptamer That Binds to the gD Protein of Herpes Simplex Virus 1 and Efficiently Inhibits Viral Entry

Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell–cell adhesion

Nanostructures/Graphene/Silicon Junction‐Based High‐Performance Photodetection Systems: Progress, Challenges, and Future Trends

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