Human neutrophil – mediated destruction of antibody sensitized herpes simplex virus type I infected cells

1978 ◽  
Vol 24 (2) ◽  
pp. 182-186 ◽  
Author(s):  
Yoshaiki Fujimiya ◽  
Barry T. Rouse ◽  
Lorne A. Babiuk
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Peripheral Blood ◽  
Polymorphonuclear Neutrophils ◽  
Target Cells ◽  
Type I ◽  
Effector Cells ◽  
Ability To Act ◽  
Simplex Virus

Human peripheral blood polymorphonuclear neutrophils (PMN) were tested for their ability to act as effector cells in antibody-dependent cell cytotoxicity (ADCC) against Herpes simplex virus (HSV) infected target cells sensitized with anti-HSV serum. The PMN from all 29 individuals tested could mediate ADCC in the presence of a standard human anti-HSV serum. Since PMN are prominent cells early in herpes lesions, it was hypothesized that because ADCC could represent an in vitro model for antiviral recovery, perhaps the efficacy of PMN at mediating ADCC might be impaired in those subject to frequent recrudescent herpes. However, evidence for the hypothesis was not obtained since the PMN from individuals with frequent, infrequent, or unrecorded herpes labialis all showed approximately the same activity at mediating ADCC. Alternative ways in which PMN could be involved in antiviral recovery were discussed.

scholarly journals ASC-dependent inflammasomes contribute to immunopathology and mortality in herpes simplex encephalitis

2021 ◽  
Vol 17 (2) ◽  
pp. e1009285
Author(s):  
Cooper K. Hayes ◽  
Douglas R. Wilcox ◽  
Yuchen Yang ◽  
Grace K. Coleman ◽  
Melissa A. Brown ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Replication ◽  
Adaptor Protein ◽  
Herpes Simplex Virus Encephalitis ◽  
Inflammasome Activation ◽  
Type I ◽  
Simplex Virus ◽  
The Brain

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis, and despite targeted antiviral therapy, outcomes remain poor. Although the innate immune system is critical for restricting herpes simplex virus type I (HSV-1) in the brain, there is evidence that prolonged neuroinflammation contributes to HSE pathogenesis. In this study, we investigated the contribution of inflammasomes to disease pathogenesis in a murine model of HSE. Inflammasomes are signaling platforms that activate the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. We found that mice deficient in the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), had significantly improved survival and lower levels of IL-1β and IL-18 in the brain. Importantly, this difference in survival was independent of viral replication in the central nervous system (CNS). We found that microglia, the resident macrophages of the CNS, are the primary mediators of the ASC-dependent inflammasome response during infection. Using in vitro glial infections and a murine HSE model, we demonstrate that inflammasome activation contributes to the expression of chemokine (C-C motif) ligand 6 (CCL6), a leukocyte chemoattractant. The lower concentration of CCL6 in the brains of ASC-/- mice correlated with lower numbers of infiltrating macrophages during infection. Together, these data suggest that inflammasomes contribute to pathogenic inflammation in HSE and provide a mechanistic link between glial inflammasome activation and leukocyte infiltration. The contribution of inflammasomes to survival was independent of viral replication in our study, suggesting a promising new target in combating harmful inflammation in HSE.

scholarly journals Antiviral Properties of R. tanguticum Nanoparticles on Herpes Simplex Virus Type I In Vitro and In Vivo

2019 ◽  
Vol 10 ◽  
Author(s):  
Meng-xin Shen ◽  
Nian Ma ◽  
Min-ke Li ◽  
Yuan-yuan Liu ◽  
Tian Chen ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Type I ◽  
Simplex Virus

scholarly journals Inhibition of Herpes Simplex Virus Type 1 and Type 2 Infections by Peptide-Derivatized Dendrimers

2011 ◽  
Vol 55 (7) ◽  
pp. 3231-3239 ◽  
Author(s):  
Anna Luganini ◽  
Silvia Fabiole Nicoletto ◽  
Lorena Pizzuto ◽  
Giovanna Pirri ◽  
Andrea Giuliani ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Serum Proteins ◽  
Antiviral Agents ◽  
Target Cells ◽  
Synergistic Activity ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTIn response to the need for new antiviral agents, dendrimer-based molecules have been recognized as having a large number of potential therapeutic applications. They include peptide-derivatized dendrimers, which are hyperbranched synthetic well-defined molecules which consist of a peptidyl branching core and covalently attached surface functional peptides. However, few studies have addressed their applications as direct-acting antiviral agents. Here, we report on the ability of the peptide dendrimer SB105 and its derivative, SB105_A10, to directly inhibit herpes simplex virus 1 (HSV-1) and HSV-2in vitroreplication, with favorable selective indexes discerned for both compounds. An analysis of their mode of action revealed that SB105 and SB105_A10 prevent HSV-1 and HSV-2 attachment to target cells, whereas SB104, a dendrimer with a different amino acid sequence within the functional group and minimal antiviral activity, was ineffective in blocking HSV attachment. Moreover, both SB105 and SB105_A10 retained their ability to inhibit HSV adsorption at pH 3.0 and 4.0 and in the presence of 10% human serum proteins, conditions mimicking the physiological properties of the vagina, a potential therapeutic location for such compounds. The inhibition of HSV adsorption is likely to stem from the ability of SB105_A10 to bind to the glycosaminoglycan moiety of cell surface heparan sulfate proteoglycans, thereby blocking virion attachment to target cells. Finally, when combined with acyclovir in checkerboard experiments SB105_A10 exhibited highly synergistic activity. Taken together, these findings suggest that SB105 and SB105_A10 are promising candidates for the development of novel topical microbicides for the prevention of HSV infections.

Inactivation of Herpes Simplex Virus by Photosensitizing Anthraquinones Isolated from Heterophyllaea pustulata

Planta Medica ◽  
2021 ◽  
Author(s):  
M. Laura Mugas ◽  
Juliana Marioni ◽  
Florencia Martinez ◽  
Juan J. Aguilar ◽  
José L. Cabrera ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Antiviral Effect ◽  
Neutral Red ◽  
Host Cells ◽  
Type I ◽  
Antiherpetic Activity ◽  
Simplex Virus

Abstract Heterophyllaea pustulata is a phototoxic plant from Argentina. Aerial parts extracts, high in photosensitizing anthraquinones, have shown in vitro antiviral activity. The purpose of this study was to study the antiherpetic activity of the main purified anthraquinones, even evaluating their competence as photodynamic sensitizers to photo-stimulate the antiviral effect. In vitro antiviral activity against Herpes Simplex virus type I and the photo-inactivation of viral particle were studied by the Neutral Red uptake test and observation of the cytopathic effect. Rubiadin 1-methyl ether and 5,5′-bisoranjidiol produced a significant effect (≥ 80% inhibition) with minimal damage to host cells (subtoxic concentration). Anthraquinones with poor antiherpetic activity at its maximum noncytotoxic concentration showed an important photo-stimulated effect, such is the case of soranjidiol and 5,5′-bisoranjidiol (28.0 ± 6.3 vs. 81.8 ± 2.1% and 15.5 ± 0.3 vs. 89.8 ± 1.7%, respectively). The study also proved the decrease of viral particles, necessary to reduce infection. Therefore, photosensitizing anthraquinones from natural resources could be proposed to develop new treatments for localized viral lesions with antimicrobial photodynamic therapy.

scholarly journals Antiviral and Cytotoxic Activities of Polysaccharides Extracted from Four Tropical Seaweed Species

2017 ◽  
Vol 12 (6) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Gilles Bedoux ◽  
Edgar Caamal-Fuentes ◽  
Romain Boulho ◽  
Christel Marty ◽  
Nathalie Bourgougnon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Cytotoxic Activities ◽  
Type I ◽  
Chemical Structures ◽  
Antiviral Activities ◽  
Simplex Virus ◽  
Solieria Filiformis

Polysaccharides extracted from Rhodymenia pseudopalmata, Solieria filiformis, Hydropuntia cornea (Rhodophyta) and Sargassum fluitans (Phaeophyceae) were evaluated for its cytotoxic and antiviral activities against Herpes simplex virus (HSV-Type 1). Chemical structures were characterized by FT-IR spectroscopy and 13C-NMR analyses. Polysaccharides from Sargassum fluitans (EC50 = 42.8 μg/ml) and Solieria filiformis (EC50 = 136.0 μg/ml) showed antiviral activity against herpes simplex virus type-I in vitro at a multiplicity of infection (MOI) of 0.01 ID50/cells without cytotoxicity (1–200 μg/mL). The activity observed suggests that sulphation, molecular weight and carbohydrate nature of these polysaccharides may be involved in this activity. To better understand the antiviral activity of the polysaccharides evaluated, it seems important to study the mechanism of action involved. These polysaccharides could be studied further to evaluate their potential use as antiviral drugs.

scholarly journals Activity and Mechanism of Action of N-Methanocarbathymidine against Herpesvirus and Orthopoxvirus Infections

2006 ◽  
Vol 50 (4) ◽  
pp. 1336-1341 ◽  
Author(s):  
Mark N. Prichard ◽  
Kathy A. Keith ◽  
Debra C. Quenelle ◽  
Earl R. Kern
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mechanism Of Action ◽  
Type I ◽  
Viral Dna ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

ABSTRACT N-Methanocarbathymidine [(N)-MCT] is a conformationally locked nucleoside analog that is active against some herpesviruses and orthopoxviruses in vitro. The antiviral activity of this molecule is dependent on the type I thymidine kinase (TK) in herpes simplex virus and also appears to be dependent on the type II TK expressed by cowpox and vaccinia viruses, suggesting that it is a substrate for both of these divergent forms of the enzyme. The drug is also a good inhibitor of viral DNA synthesis in both viruses and is consistent with inhibition of the viral DNA polymerase once it is activated by the viral TK homologs. This mechanism of action explains the rather unusual spectrum of activity, which is limited to orthopoxviruses, alphaherpesviruses, and Epstein-Barr virus, since these viruses express molecules with TK activity that can phosphorylate and thus activate the drug. The compound is also effective in vivo and reduces the mortality of mice infected with orthopoxviruses, as well as those infected with herpes simplex virus type 1 when treatment is initiated 24 h after infection. These results indicate that (N)-MCT is active in vitro and in vivo, and its mechanism of action suggests that the molecule may be an effective therapeutic for orthopoxvirus and herpesvirus infections, thus warranting further development.

scholarly journals Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Derek J. Royer ◽  
Meghan M. Carr ◽  
Ana J. Chucair-Elliott ◽  
William P. Halford ◽  
Daniel J. J. Carr
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Parental Strain ◽  
Vaccine Development ◽  
Viral Fitness ◽  
Type I ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Viral fitness dictates virulence and capacity to evade host immune defenses. Understanding the biological underpinnings of such features is essential for rational vaccine development. We have previously shown that the live-attenuated herpes simplex virus 1 (HSV-1) mutant lacking the nuclear localization signal (NLS) on the ICP0 gene (0ΔNLS) is sensitive to inhibition by interferon beta (IFN-β) in vitro and functions as a highly efficacious experimental vaccine. Here, we characterize the host immune response and in vivo pathogenesis of HSV-1 0ΔNLS relative to its fully virulent parental strain in C57BL/6 mice. Additionally, we explore the role of type 1 interferon (IFN-α/β) signaling on virulence and immunogenicity of HSV-1 0ΔNLS and uncover a probable sex bias in the induction of IFN-α/β in the cornea during HSV-1 infection. Our data show that HSV-1 0ΔNLS lacks neurovirulence even in highly immunocompromised mice lacking the IFN-α/β receptor. These studies support the translational viability of the HSV-1 0ΔNLS vaccine strain by demonstrating that, while it is comparable to a virulent parental strain in terms of immunogenicity, HSV-1 0ΔNLS does not induce significant tissue pathology. IMPORTANCE HSV-1 is a common human pathogen associated with a variety of clinical presentations ranging in severity from periodic “cold sores” to lethal encephalitis. Despite the consistent failures of HSV subunit vaccines in clinical trials spanning the past 28 years, opposition to live-attenuated HSV vaccines predicated on unfounded safety concerns currently limits their widespread acceptance. Here, we demonstrate that a live-attenuated HSV-1 vaccine has great translational potential.

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