Contortrostatin, a Homodimeric Disintegrin Isolated from Snake Venom Inhibits Herpes Simplex Virus Entry and Cell Fusion

Hubbard, Stephen; Choudhary, Samiksha; Maus, Erika; Shukla, Deepak; Swenson, Stephen D.; Markland, Francis S.; Tiwari, Vaibhav

doi:10.3851/imp2291

Cited by 14 publications

(11 citation statements)

References 31 publications

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“…Recombinant spread-deficient, entry proficient strains of HSV-1(KOS) gL86 and HSV-2 (KOS) 333gJ − encoding a beta-galactosidase reporter activity were used [ 3 , 37 , 68 , 74 ]. Both virus strains enter and replicate, thus have the potential to induce cell signaling, but lack the genes essential for viral cell-to-cell spread.…”

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus (HSV) Modulation of Staphylococcus aureus and Candida albicans Initiation of HeLa 299 Cell-Associated Biofilm

et al. 2016

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Although herpes simplex virus type-1 (HSV-1), and type-2 (HSV-2), Staphylococcus aureus and Candida albicans co-habit the oral and genital mucosa, their interaction is poorly understood. We determined the effect HSV has on bacterial and/or fungal adherence, the initial step in biofilm formation. HeLa229 cells were infected with HSV-1 (KOS) gL86 or HSV-2 (KOS) 333gJ 2 at a multiplicity of infection (MOI) of 50 and 10. S. aureus (ATCC 25923) and/or C. albicans (yeast forms or germ tube forms) were co-incubated for 30 min (37°C; 5 % CO 2 ; 5:1 organism: HeLa cell ratio; n = 16) with virus-infected HeLa cells or uninfected HeLa cell controls. Post-incubation, the monolayers were washed (3x; PBS), lysed (RIPA), and the lysate plated onto Fungisel and/or mannitol salts agar for standard colony count. The level of HeLa-associated S. aureus was significantly decreased (P \ 0.05) for both HSV-1-and HSV-2-infected cells, as compared to virus-free HeLa cell controls (38 and 59 % of control, respectively). In contrast, HSV-1 and HSV-2 significantly (P \ 0.05) enhanced HeLa cell association of C. albicans yeast forms and germ tube approximately two-fold, respectively. The effect of S. aureus on germ tube and yeast form adherence to HSV-1-and HSV-2-infected cells was specific for the Candida phenotype tested. Our study suggests that HSV, while antagonist towards S. aureus adherence enhances Candida adherence. Furthermore, the combination of the three pathogens results in S. aureus adherence that is either unaffected, or partially restored depending on both the herpes viral species and the fungal phenotype present.

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Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus (HSV) Modulation of Staphylococcus aureus and Candida albicans Initiation of HeLa 299 Cell-Associated Biofilm

et al. 2016

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“…The most common dimers of SVMPs present in venoms are undoubtedly homo- and heterodimeric disintegrins. For example, contortrostatin, a homodimeric disintegrin that displays RGD motifs in both chains, has been produced in a recombinant form [ 79 ] and presented substantial anti-angiogenic and anti-cancer effects [ 79 ] with some efficacy as an adjuvant in chemotherapy for melanoma [ 80 ] and for viral infections [ 81 ]. Heterodimers composed of distinct disintegrin domains have also been isolated.…”

Section: Biosynthesis and Post-translational Processing Of Svmpsmentioning

confidence: 99%

Processing of Snake Venom Metalloproteinases: Generation of Toxin Diversity and Enzyme Inactivation

Moura-da-Silva

Almeida

Portes-Junior

et al. 2016

Toxins

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Snake venom metalloproteinases (SVMPs) are abundant in the venoms of vipers and rattlesnakes, playing important roles for the snake adaptation to different environments, and are related to most of the pathological effects of these venoms in human victims. The effectiveness of SVMPs is greatly due to their functional diversity, targeting important physiological proteins or receptors in different tissues and in the coagulation system. Functional diversity is often related to the genetic diversification of the snake venom. In this review, we discuss some published evidence that posit that processing and post-translational modifications are great contributors for the generation of functional diversity and for maintaining latency or inactivation of enzymes belonging to this relevant family of venom toxins.

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“…In spite of their toxicological effects, several isolated snake venom proteins and peptides have practical applications as pharmaceutical agents [23]. For example, thrombolytic agents have been used in several cases of vascular disorder [24], antimicrobial activity against gram-positive and gram-negative bacteria [25, 26], antiviral activity against several types of viruses including the herpes simplex virus [27], yellow fever and dengue [28], antiparasitic activity against Leishmania [29] and Plasmodium falciparum [30], and antifungal activity [31], among other examples.…”

Section: Introductionmentioning

confidence: 99%

Antitumoral Activity of Snake Venom Proteins: New Trends in Cancer Therapy

Calderon

Sobrinho

Zaqueo

et al. 2014

BioMed Research International

163

149

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For more than half a century, cytotoxic agents have been investigated as a possible treatment for cancer. Research on animal venoms has revealed their high toxicity on tissues and cell cultures, both normal and tumoral. Snake venoms show the highest cytotoxic potential, since ophidian accidents cause a large amount of tissue damage, suggesting a promising utilization of these venoms or their components as antitumoral agents. Over the last few years, we have studied the effects of snake venoms and their isolated enzymes on tumor cell cultures. Some in vivo assays showed antineoplastic activity against induced tumors in mice. In human beings, both the crude venom and isolated enzymes revealed antitumor activities in preliminary assays, with measurable clinical responses in the advanced treatment phase. These enzymes include metalloproteases (MP), disintegrins, L-amino acid oxidases (LAAOs), C-type lectins, and phospholipases A2 (PLA2s). Their mechanisms of action include direct toxic action (PLA2s), free radical generation (LAAOs), apoptosis induction (PLA2s, MP, and LAAOs), and antiangiogenesis (disintegrins and lectins). Higher cytotoxic and cytostatic activities upon tumor cells than normal cells suggest the possibility for clinical applications. Further studies should be conducted to ensure the efficacy and safety of different snake venom compounds for cancer drug development.

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Contortrostatin, a Homodimeric Disintegrin Isolated from Snake Venom Inhibits Herpes Simplex Virus Entry and Cell Fusion

Abstract: CN, a novel venom-derived peptide, exhibits the ability to block two key steps, entry and cell-to-cell fusion, in HSV infection. Showing strong promise for development as an anti-HSV agent, it also demonstrates better prophylactic efficacy in primary cells.

Cited by 14 publications

References 31 publications

Herpes Simplex Virus (HSV) Modulation of Staphylococcus aureus and Candida albicans Initiation of HeLa 299 Cell-Associated Biofilm

Herpes Simplex Virus (HSV) Modulation of Staphylococcus aureus and Candida albicans Initiation of HeLa 299 Cell-Associated Biofilm

Processing of Snake Venom Metalloproteinases: Generation of Toxin Diversity and Enzyme Inactivation

Antitumoral Activity of Snake Venom Proteins: New Trends in Cancer Therapy

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