Varicella-Zoster Virus Glycoproteins: Entry, Replication, and Pathogenesis

Oliver, Stefan L.; Yang, Edward; Arvin, Ann M.

doi:10.1007/s40588-016-0044-4

Cited by 41 publications

(37 citation statements)

References 100 publications

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“…After dissemination VZV infects neurons via the axonal termini or cell body 45 . In addition VZV lacks the receptor binding member of the receptor complex, gD, and is highly cell associated with the generation of very few free virus particles 46 . Using data generated in this paper, a future focus of research will be to test the function of both conserved and divergent residues of gK across multiple families of alphaherpesvirus species.…”

Section: Discussionmentioning

confidence: 99%

Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling

Rider

Coghill

Naderi

et al. 2019

Sci Rep

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Alphaherpesviruses are a subfamily of herpesviruses that include the significant human pathogens herpes simplex viruses (HSV) and varicella zoster virus (VZV). Glycoprotein K (gK), conserved in all alphaherpesviruses, is a multi-membrane spanning virion glycoprotein essential for virus entry into neuronal axons, virion assembly, and pathogenesis. Despite these critical functions, little is known about which gK domains and residues are most important for maintaining these functions across all alphaherpesviruses. Herein, we employed phylogenetic and structural analyses including the use of a novel model for evolutionary rate variation across residues to predict conserved gK functional domains. We found marked heterogeneity in the evolutionary rate at the level of both individual residues and domains, presumably as a result of varying selective constraints. To clarify the potential role of conserved sequence features, we predicted the structures of several gK orthologs. Congruent with our phylogenetic analysis, slowly evolving residues were identified at potentially structurally significant positions across domains. We found that using a quantitative measure of amino acid rate variation combined with molecular modeling we were able to identify amino acids predicted to be critical for gK protein structure/function. This analysis yields targets for the design of anti-herpesvirus therapeutic strategies across all alphaherpesvirus species that would be absent from more traditional analyses of conservation.

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Section: Discussionmentioning

confidence: 99%

Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling

Rider

Coghill

Naderi

et al. 2019

Sci Rep

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“…The lipid envelope of VZV contains numerous glycoproteins that are required for replication and pathogenesis [343]. VZV glycoprotein C activity facilitates the recruitment and subsequent infection of leukocytes, increases chemokine mediated leukocyte migration and hence enhances VZV systemic dissemination in humans [333].…”

Section: Glycoproteinsmentioning

confidence: 99%

“…Glycoproteins B and E might form the basis for novel non-hazardous subunit vaccines suitable for immunocompromised hosts [311]. The cytoplasmic domain lysine cluster of VZV glycoprotein B is implicated in the regulation of glycoprotein B fusion, ultimately leading to attenuation of VZV infection if unmodulated, so this domain is critical for the regulation of VZV cell to cell fusion and VZV infection [343,344]. VZV glycoprotein M is important for ef icient cell to cell virus spread but it is not essential for virus growth [345].…”

Section: Glycoproteinsmentioning

confidence: 99%

“…The various elements that are implicated in VZV infections are illustrated in igure 3. [101,[204][205][206][207]245,248,268,[272][273][274]276,292,[304][305][306][307][310][311][312][313][320][321][322][323][324]334,341,[343][344][345][346]349,350,361,[368][369][370][371]378,381,387,[397][398][399][400][401][402][403][404]…”

Section: Other Signaling Pathways In Vzv Infectionmentioning

confidence: 99%

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The beneficial effects of varicella zoster virus

Al-Anazi¹,

Wk²,

Al-Jasser³

2019

J Hematol Clin Res

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Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the benefi cial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported benefi cial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.

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“…Thus, they are attractive targets for antiviral drug development. 3 VZV gE among VZV glycoproteins is the most abundant and immunogenic. It participates in viral replication and cell-cell transmission.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant

Lee

Park

et al. 2020

Immunity Inflam & Disease

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Introduction: Varicella-zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. A live attenuated vaccine (LAV) and glycoprotein E (gE) subunit vaccine were developed to prevent VZV-induced diseases. We recently reported that single-strand RNA (ssRNA) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (CrPV) is an effective adjuvant for protein-based and virus-like particle-based vaccines. Here, Chinese hamster ovary expression system and an LAV from Oka/SK strains. Methods: We appraised the adjuvant effect of the same CrPV ssRNA encoding the gE gene formulated in the two vaccines using VZV-primed C57BL/6 mice and guinea pigs. Humoral immunity and cell-mediated immunity were assessed by enzyme-linked immunosorbent assay (ELISA) and ELISPOT in gE subunit vaccine and by ELISA and fluorescent antibody to membrane antigen in LAV. Results: The gE subunit vaccine-induced gE-specific antibodies and CD4 + T-cell responses (indicated by interferon-γ [IFN-γ] and interleukin-2 secretion) in the ssRNA-based adjuvant containing the VZV gE gene. Therefore, an ssRNA adjuvant combined with gE antigen can trigger the innate immune response and induce an adaptive immune response to ultimately activate humoral and cell-mediated responses. VZV LAV could also induce VZV-specific antibodies and IFN-γ stimulated by LAV, whereas the effect of ssRNA as a ---This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. contributed equally to this study.vaccine adjuvant could not be confirmed. However, the ssRNA adjuvant increased VZV-specific neutralizing antibody response. Conclusions: Taken together, these results highlight that the gE subunit vaccine and LAV developed in this study can be functional VZV vaccines, and ssRNAs appear to function better as adjuvants in a subunit vaccine than in an LAV. K E Y W O R D S chickenpox, gE subunit vaccine, live attenuated vaccine, RNA adjuvant, shingles, varicella-zoster virus

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Varicella-Zoster Virus Glycoproteins: Entry, Replication, and Pathogenesis

Cited by 41 publications

References 100 publications

Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling

Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling

The beneficial effects of varicella zoster virus

Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant

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