Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity

Herold, Betsy C.; WuDunn, Darrell; Soltys, Nanette; Spear, Patricia G.

doi:10.1128/jvi.65.3.1090-1098.1991

Cited by 508 publications

(294 citation statements)

References 48 publications

(73 reference statements)

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“…The most extensively characterized HSV glycoprotein, with respect to its N-and O-linked glycosylations, is HSV-1 gC (gC-1), which contains nine sites for N-linked glycosylation and numerous clusters of O-linked glycans (46). However, while gC-1 mediates binding of HSV-1 to heparan sulfate and is involved in immune evasion through its interactions with complement components, it is not required for cell-to-cell spread (47). Moreover, for HSV-2, gB-2, not gC-2, plays the major role in promoting viral binding, and gC-2 is dispensable for viral infection in cell culture (48).…”

Section: Discussionmentioning

confidence: 99%

Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread

Nixon

Stefanidou

Mesquita

et al. 2013

J Virol

152

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e Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P < 0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.

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Section: Discussionmentioning

confidence: 99%

Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread

Nixon

Stefanidou

Mesquita

et al. 2013

J Virol

152

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“…Since both BRACO-19 and TMPyP2, as most G-quadruplex binding molecules, are polycationic agents, we first excluded that the observed antiviral activity was due to the interaction of these molecules with the negatively charged heparan sulfate (Campadelli-Fiume et al, 2007;Herold et al, 1991), thus preventing virus attachment to the cells. BRACO-19 or TMPyP2 were added at different times relative to infection until the virus had completed its entry into cells (i.e.…”

Section: Braco-19 Does Not Inhibit Viral Entry Into Cellsmentioning

confidence: 99%

The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand

et al. 2015

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Guanine-rich nucleic acids can fold into G-quadruplexes, secondary structures implicated in important regulatory functions at the genomic level in humans, prokaryotes and viruses. The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. Using biophysical, molecular biology and antiviral assays, we showed that the HSV-1 genome displays multiple clusters of repeated sequences that form very stable G-quadruplexes. These sequences are mainly located in the inverted repeats of the HSV-1 genome. Treatment of HSV-1 infected cells with the G-quadruplex ligand BRACO-19 induced inhibition of virus production. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. The last step targeted by BRACO-19 was viral DNA replication, while no effect on virus entry in the cells was observed. This work, presents the first evidence of extended G-quadruplex sites in key regions of the HSV-1 genome, indicates the possibility to block viral DNA replication by G-quadruplex-ligand and therefore provides a proof of concept for the use of G-quadruplex ligands as new anti-herpetic therapeutic options.

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“…This is also the case for herpes simplex virus type 1 (HSV-1), a ubiquitous human pathogen, causing mucocutaneous lesions on lips and mouth (6) but also, in rare cases, severe encephalitis (7). Initial attachment of HSV-1 is mediated by the envelope glycoprotein gC binding to heparan sulfate (HS) (8) and chondroitin sulfate (CS) (9,10), two sulfated GAGs found on the cell surface and in the extracellular matrix. Furthermore, glycoprotein gB has been shown to take over the role of attachment protein in gC-deficient virions (11).…”

Section: Introductionmentioning

confidence: 99%

Binding Kinetics and Lateral Mobility of HSV-1 on End-Grafted Sulfated Glycosaminoglycans

Peerboom

Block

Altgärde

et al. 2017

Biophysical Journal

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Many viruses, including herpes simplex (HSV), are recruited to their host cells via interaction between their envelope glycoproteins and cell-surface glycosaminoglycans (GAGs). This initial attachment is of a multivalent nature, i.e., it requires the establishment of multiple bonds between amino acids of viral glycoproteins and sulfated saccharides on the GAG chain. To gain understanding of how this binding process is modulated, we performed binding kinetics and mobility studies using end-grafted GAG chains that mimic the end attachment of these chains to proteoglycans. Total internal reflection fluorescence microscopy was used to probe binding and release, as well as the diffusion of single HSV-1 particles. To verify the hypothesis that the degree of sulfation, but also the arrangement of sulfate groups along the GAG chain, plays a key role in HSV binding, we tested two native GAGs (chondroitin sulfate and heparan sulfate) and compared our results to chemically sulfated hyaluronan. HSV-1 recognized all sulfated GAGs, but not the nonsulfated hyaluronan, indicating that binding is specific to the presence of sulfate groups. Furthermore we observed that a notable fraction of GAG-bound virions exhibit lateral mobility, although the multivalent binding to the immobilized GAG brushes ensures firm virus attachment to the interface. Diffusion was faster on the two native GAGs, one of which, chondroitin sulfate, was also characterized by the highest association rate per GAG chain. This highlights the complexity of multivalent virus-GAG interactions and suggests that the spatial arrangement of sulfates along native GAG chains may play a role in modulating the characteristics of the HSV-GAG interaction. Altogether, these results, obtained with a minimal and well-controlled model of the cell membrane, provide, to our knowledge, new insights into the dynamics of the HSV-GAG interaction.

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Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity

Cited by 508 publications

References 48 publications

Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread

Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread

The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand

Binding Kinetics and Lateral Mobility of HSV-1 on End-Grafted Sulfated Glycosaminoglycans

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