scholarly journals Antiherpes Effect of Dextran Sulphate Combined with Acyclovir in vitro and in vivo

1993 ◽  
Vol 4 (3) ◽  
pp. 189-191 ◽  
Author(s):  
S. N. Pancheva
Keyword(s):  
Herpes Simplex ◽  
Pseudorabies Virus ◽  
Antiviral Effect ◽  
Yield Reduction ◽  
Ocular Infection ◽  
Dextran Sulphate ◽  
Virus Shedding ◽  
Hsv 1

The combined antiviral effect of dextran sulphate (DS, MW 40000) and acyclovir (ACV) on herpes simplex virus type 1 (HSV-1) and Pseudorabies virus (PRV) in vitro and on experimental HSV-1 keratitis in rabbits, was studied. Dextran sulphate in combination with ACV results in synergistic effect, as measured by yield reduction assay and on herpes simplex keratitis in rabbits. The better therapeutic effect of the combination was proved by the decreased severity of ocular infection and the reduction of the virus shedding in tear film.

scholarly journals Structural Variability of the Herpes Simplex Virus 1 GenomeIn VitroandIn Vivo

2012 ◽  
Vol 86 (16) ◽  
pp. 8592-8601 ◽  
Author(s):  
Charlotte Mahiet ◽  
Ayla Ergani ◽  
Nicolas Huot ◽  
Nicolas Alende ◽  
Ahmed Azough ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Considerable Proportion ◽  
Inverted Repeats ◽  
Herpes Simplex Virus 1 ◽  
Cell Extracts ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus 1 (HSV-1) is a human pathogen that leads to recurrent facial-oral lesions. Its 152-kb genome is organized in two covalently linked segments, each composed of a unique sequence flanked by inverted repeats. Replication of the HSV-1 genome produces concatemeric molecules in which homologous recombination events occur between the inverted repeats. This mechanism leads to four genome isomers (termed P, IS, IL, and ILS) that differ in the relative orientations of their unique fragments. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Using fluorescence hybridization, isomers were repeatedly detected and distinguished and were accompanied by a large proportion of noncanonical forms (40%). In both cell and viral-particle extracts, the distributions of the four isomers were statistically equivalent, except for strain KOS grown in Vero and Neuro-2a cells, in which P and IS isomers were significantly overrepresented. In infected cell extracts, concatemeric molecules as long as 10 genome equivalents were detected, among which, strikingly, the isomer distributions were equivalent, suggesting that any such imbalance may occur during encapsidation.In vivo, for strain KOS-infected trigeminal ganglia, an unbalanced distribution distinct from the onein vitrowas observed, along with a considerable proportion of noncanonical assortment.

scholarly journals Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo.

1995 ◽  
Vol 39 (4) ◽  
pp. 846-849 ◽  
Author(s):  
H Aoki ◽  
T Akaike ◽  
K Abe ◽  
M Kuroda ◽  
S Arai ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Rice Seed ◽  
Simplex Virus ◽  
Hsv 1

Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1.

scholarly journals Restoring Herpesvirus Entry Mediator (HVEM) Immune Function in HVEM−/− Mice Rescues Herpes Simplex Virus 1 Latency and Reactivation Independently of Binding to Glycoprotein D

2020 ◽  
Vol 94 (16) ◽  
Author(s):  
Kati Tormanen ◽  
Shaohui Wang ◽  
Ujjaldeep Jaggi ◽  
Homayon Ghiasi
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Function ◽  
Interleukin 2 ◽  
Glycoprotein D ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The immune modulatory protein herpes virus entry mediator (HVEM) is one of several cellular receptors used by herpes simplex virus 1 (HSV-1) for cell entry. HVEM binds to HSV-1 glycoprotein D (gD) but is not necessary for HSV-1 replication in vitro or in vivo. Previously, we showed that although HSV-1 replication was similar in wild-type (WT) control and HVEM−/− mice, HSV-1 does not establish latency or reactivate effectively in mice lacking HVEM, suggesting that HVEM is important for these functions. It is not known whether HVEM immunomodulatory functions contribute to latency and reactivation or whether its binding to gD is necessary. We used HVEM−/− mice to establish three transgenic mouse lines that express either human WT HVEM or human or mouse HVEM with a point mutation that ablates its ability to bind to gD. Here, we show that HVEM immune function, not its ability to bind gD, is required for WT levels of latency and reactivation. We further show that HVEM binding to gD does not affect expression of the HVEM ligands BTLA, CD160, or LIGHT. Interestingly, our results suggest that binding of HVEM to gD may contribute to efficient upregulation of CD8α but not PD1, TIM-3, CTLA4, or interleukin 2 (IL-2). Together, our results establish that HVEM immune function, not binding to gD, mediates establishment of latency and reactivation. IMPORTANCE HSV-1 is a common cause of ocular infections worldwide and a significant cause of preventable blindness. Corneal scarring and blindness are consequences of the immune response induced by repeated reactivation events. Therefore, HSV-1 therapeutic approaches should focus on preventing latency and reactivation. Our data suggest that the immune function of HVEM plays an important role in the HSV-1 latency and reactivation cycle that is independent of HVEM binding to gD.

scholarly journals CD80 Plays a Critical Role in Increased Inflammatory Responses in Herpes Simplex Virus 1-Infected Mouse Corneas

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Kati Tormanen ◽  
Shaohui Wang ◽  
Homayon Ghiasi
Keyword(s):  
T Cells ◽  
Herpes Simplex ◽  
Parental Virus ◽  
Eye Disease ◽  
Herpes Simplex Virus 1 ◽  
Corneal Scarring ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT We recently reported that herpes simplex virus 1 (HSV-1) infection suppresses CD80 but not CD86 expression in vitro and in vivo. This suppression required the HSV-1 ICP22 gene. We also reported that overexpression of CD80 by HSV-1 exacerbated corneal scarring in BALB/c mice. We now show that this recombinant virus (HSV-CD80) expressed high levels of CD80 both in vitro in cultured rabbit skin cells and in vivo in infected mouse corneas. CD80 protein was detected on the surface of infected cells. The virulence of the recombinant HSV-CD80 virus was similar to that of the parental strain, and the replication of HSV-CD80 was similar to that of control virus in vitro and in vivo. Transcriptome analysis detected 75 known HSV-1 genes in the corneas of mice infected with HSV-CD80 or parental virus on day 4 postinfection. Except for significantly higher CD80 expression in HSV-CD80-infected mice, levels of HSV-1 gene expression were similar in corneas from HSV-CD80-infected and parental virus-infected mice. The number of CD8+ T cells was higher, and the number of CD4+ T cells was lower, in the corneas of HSV-CD80-infected mice than in mice infected with parental virus. HSV-CD80-infected mice displayed a transient increase in dendritic cells. Transcriptome analysis revealed mild differences in dendritic cell maturation and interleukin-1 signaling pathways and increased expression of interferon-induced protein with tetratricopeptide repeats 2 (Ifit2). Together, these results suggest that increased CD80 levels promote increased CD8+ T cells, leading to exacerbated eye disease in HSV-1-infected mice. IMPORTANCE HSV-1 ocular infections are the leading cause of corneal blindness. Eye disease is the result of a prolonged immune response to the replicating virus. HSV-1, on the other hand, has evolved several mechanisms to evade clearance by the host immune system. We describe a novel mechanism of HSV-1 immune evasion via ICP22-dependent downregulation of the host T cell costimulatory molecule CD80. However, the exact role of CD80 in HSV-1 immune pathology is not clear. In this study, we show that eye disease is independent of the level of HSV-1 replication and that viral expression of CD80 has a detrimental role in corneal scarring, likely by increasing CD8+ T cell recruitment and activation.

scholarly journals Alpha/Beta Interferon and Gamma Interferon Synergize To Inhibit the Replication of Herpes Simplex Virus Type 1

2002 ◽  
Vol 76 (22) ◽  
pp. 11541-11550 ◽  
Author(s):  
Bruno Sainz ◽  
William P. Halford
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Vero Cells ◽  
Ifn Γ ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT In vivo evidence suggests that T-cell-derived gamma interferon (IFN-γ) can directly inhibit the replication of herpes simplex virus type 1 (HSV-1). However, IFN-γ is a weak inhibitor of HSV-1 replication in vitro. We have found that IFN-γ synergizes with the innate IFNs (IFN-α and -β) to potently inhibit HSV-1 replication in vitro and in vivo. Treatment of Vero cells with either IFN-β or IFN-γ inhibits HSV-1 replication by <20-fold, whereas treatment with both IFN-β and IFN-γ inhibits HSV-1 replication by ∼1,000-fold. Treatment with IFN-β and IFN-γ does not prevent HSV-1 entry into Vero cells, and the inhibitory effect can be overcome by increasing the multiplicity of HSV-1 infection. The capacity of IFN-β and IFN-γ to synergistically inhibit HSV-1 replication is not virus strain specific and has been observed in three different cell types. For two of the three virus strains tested, IFN-β and IFN-γ inhibit HSV-1 replication with a potency that approaches that achieved by a high dose of acyclovir. Pretreatment of mouse eyes with IFN-β and IFN-γ reduces HSV-1 replication to nearly undetectable levels, prevents the development of disease, and reduces the latent HSV-1 genome load per trigeminal ganglion by ∼200-fold. Thus, simultaneous activation of IFN-α/β receptors and IFN-γ receptors appears to render cells highly resistant to the replication of HSV-1. Because IFN-α or IFN-β is produced by most cells as an innate response to virus infection, the results imply that IFN-γ secreted by T cells may provide a critical second signal that potently inhibits HSV-1 replication in vivo.

scholarly journals A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Olus Uyar ◽  
Pier-Luc Plante ◽  
Jocelyne Piret ◽  
Marie-Christine Venable ◽  
Julie Carbonneau ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Culture Supernatant ◽  
Herpes Simplex Virus Encephalitis ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1 ◽  
Viral Titers

AbstractHerpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.

scholarly journals Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

2021 ◽  
pp. 362-368
Author(s):  
Gislaine Franco de Moura- Costa ◽  
Gean Pier Panizzon ◽  
Thalita Zago Oliveira ◽  
Marco Antonio Costa ◽  
João Carlos Palazzo de Mello ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Biological Activities ◽  
Leaf Extracts ◽  
In Vivo Toxicity ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

A Comparative Study of the in vitro and in vivo Antiviral Activities of Acyclovir and Penciclovir

1995 ◽  
Vol 6 (2) ◽  
pp. 89-97 ◽  
Author(s):  
P. Ertl ◽  
W. Snowden ◽  
D. Lowe ◽  
W. Miller ◽  
P. Collins ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Varicella Zoster ◽  
Significant Difference ◽  
Simplex Virus ◽  
Hsv 1

The antiviral properties of the compounds acyclovir (ACV) and penciclovir (PCV) have been compared in a number of in vitro and in vivo assays. In vitro, both compounds had good activity against herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV), although ACV showed statistically significant superiority. In addition, ACV had greater activity against herpes simplex virus type 2 (HSV-2), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). We examined the effect of time of addition and removal of ACV and PCV under a variety of conditions and found similar results with the two compounds under most conditions. However, at a high multiplicity of infection, when all of the cells would be expected to be synchronously expressing large amounts of the viral thymidine kinase, short exposures to PCV appeared to be superior to similar exposures to ACV. In the HSV-1 zosteriform mouse model there was no significant difference between the activities of ACV and PCV, or its prodrug famciclovir (FCV), in once- or twice-daily treatment. The possible significance of these results and those previously reported on the activity of the compounds in humans is discussed.

scholarly journals Review of Whole Plant Extracts With Activity Against Herpes Simplex Viruses In Vitro and In Vivo

2021 ◽  
Vol 26 ◽  
pp. 2515690X2097839
Author(s):  
Anna Garber ◽  
Lianna Barnard ◽  
Chris Pickrell
Keyword(s):  
Herpes Simplex ◽  
Plant Extracts ◽  
Animal Cell ◽  
Model Design ◽  
Herpes Simplex Viruses ◽  
Whole Plant ◽  
Antiviral Medications ◽  
Hsv 1

Herpes simplex viruses, HSV-1 and HSV-2, are highly contagious and cause lifelong, latent infections with recurrent outbreaks of oral and/or genital lesions. No cure exists for HSV-1 or HSV-2 infections, but antiviral medications are commonly used to prevent and treat outbreaks. Resistance to antivirals has begun to emerge, placing an importance on finding new and effective therapies for prophylaxis and treatment of HSV outbreaks. Botanicals may be effective HSV therapies as the constituents they contain act through a variety of mechanisms, potentially making the development of antiviral resistance more challenging. A wide variety of plants from different regions in the world have been studied for antiviral activity against HSV-1 and/or HSV-2 and showed efficacy of varying degrees. The purpose of this review is to summarize research conducted on whole plant extracts against HSV-1 and/or HSV-2 in vitro and in vivo. The majority of the research reviewed was conducted in vitro using animal cell lines, and some studies used an animal model design. Also summarized are a limited number of human trials conducted using botanical therapies on HSV lesions.

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