scholarly journals Antiviral Action of Synthetic Stigmasterol Derivatives on Herpes Simplex Virus Replication in Nervous CellsIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Erina Petrera ◽  
Analía G. Níttolo ◽  
Laura E. Alché
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Antiviral Effect ◽  
Treatment Modalities ◽  
Virus Propagation ◽  
Viral Origin ◽  
Anti Inflammatory ◽  
Simplex Virus ◽  
Hsv 1

Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds1and2have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied.

Further Characterization of the Potent and Prolonged Inhibition of Herpes Simplex Virus Replication in Human Cell Lines by Penciclovir

1996 ◽  
Vol 7 (3) ◽  
pp. 128-137 ◽  
Author(s):  
T.H. Bacon ◽  
B.A. Howard
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Virus Replication ◽  
Human Cell ◽  
Human Cell Lines ◽  
Potent Inhibition ◽  
Multiple Cycles ◽  
Simplex Virus ◽  
Hsv 1

The replication of herpes simplex virus type 1 (HSV-1) or HSV-2 in MRC-5 cells infected at 0.01 pfu cell−1 treated continuously for 72 h, was inhibited more efficiently by penciclovir than aciclovir ( p = 0.0001). However, multiple cycles of replication were required in order to distinguish the compounds. Virus from cultures treated for 72 h with either compound, at 3 or 10 μg ml−1 was resistant to penciclovir and aciclovir (50% effective concentrations > 10 μg ml−1), but infectivity titres of supernatants from these aciclovirtreated cultures were higher than for penciclovir. Increased production of resistant virus in aciclovirtreated cultures may be the consequence of the less potent inhibition of virus replication by aciclovir. Penciclovir caused prolonged inhibition of HSV-1 and HSV-2 replication in three human cell lines infected at 1 pfu cell−1 following treatment for 18 h, whereas virus replication resumed rapidly after withdrawal of aciclovir. Neither compound showed prolonged activity after 18 h treatment, when the multiplicity of infection was reduced to 0.01 pfu cell−1. This surprising observation prompted experiments testing the effect of repeated pulse treatment in cultures infected at low multiplicity. Penciclovir inhibited HSV-1 replication significantly more effectively than aciclovir in MRC-5 cells infected at 10−4 pfu cell−1 treated daily for 6 h ( p < 0.001, n = 5) but only a trend was observed for HSV-2 ( p = 0.06, n = 6).

scholarly journals Combinations of Antiviral and Anti-Inflammatory Preparations for the Topical Treatment of Herpes Simplex Virus Assessed using a Murine Zosteriform Infection Model

1998 ◽  
Vol 9 (1) ◽  
pp. 19-24 ◽  
Author(s):  
AR Awan ◽  
J Harmenberg ◽  
O Flink ◽  
HJ Field
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Immune Cells ◽  
Clinical Signs ◽  
Infection Model ◽  
Virus Clearance ◽  
Anti Inflammatory ◽  
Simplex Virus ◽  
Hsv 1

Recently we have reported a zosteriform murine infection model which employs the adoptive transfer of immune cells (ATI) to recipient infected mice to produce a disease that mimics human recurrent herpes simplex virus (HSV) disease. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received immune cells from HSV-1-infected syngeneic mice. Although virus was cleared more quickly from the target tissues of virus replication in recipient mice, ATI resulted in a heightened inflammatory response and delayed healing. This model was used to test the effects of topical formulations containing foscarnet and/or the anti-inflammatory agent, hydrocortisone. Virus clearance and clinical signs, including ear thickness and zosteriform spread of lesions, were studied. Treatment with 3% foscarnet accelerated virus clearance but had little effect on clinical parameters. By contrast, 0.5% hydrocortisone increased the titre and extended the presence of infectious virus for at least 6 days, although the reduction in clinical signs was greater than that obtained with topical foscarnet. Foscarnet in combination with hydrocortisone produced a marked reduction in clinical signs while virus replication was reduced. These results are discussed in relation to the inflammation and discomfort experienced by patients and a possible role for anti-inflammatory formulations in the treatment of HSV reactivation episodes in man.

scholarly journals The Murine Homolog (Mph) of Human Herpesvirus Entry Protein B (HveB) Mediates Entry of Pseudorabies Virus but Not Herpes Simplex Virus Types 1 and 2

1999 ◽  
Vol 73 (5) ◽  
pp. 4493-4497 ◽  
Author(s):  
Deepak Shukla ◽  
Cynthia L. Rowe ◽  
Yanzhang Dong ◽  
Vincent R. Racaniello ◽  
Patricia G. Spear
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Pseudorabies Virus ◽  
Human Herpesvirus ◽  
Mouse Cell ◽  
Poliovirus Receptor ◽  
Simplex Virus ◽  
Protein B ◽  
Hsv 1

ABSTRACT A mouse member of the immunoglobulin superfamily, originally designated the murine poliovirus receptor homolog (Mph), was found to be a receptor for the porcine alphaherpesvirus pseudorabies virus (PRV). This mouse protein, designated here murine herpesvirus entry protein B (mHveB), is most similar to one of three related human alphaherpesvirus receptors, the one designated HveB and also known as poliovirus receptor-related protein 2. Hamster cells resistant to PRV entry became susceptible upon expression of a cDNA encoding mHveB. Anti-mHveB antibody and a soluble protein composed of the mHveB ectodomain inhibited mHveB-dependent PRV entry. Expression of mHveB mRNA was detected in a variety of mouse cell lines, but anti-mHveB antibody inhibited PRV infection in only a subset of these cell lines, indicating that mHveB is the principal mediator of PRV entry into some mouse cell types but not others. Coexpression of mHveB with PRV gD, but not herpes simplex virus type 1 (HSV-1) gD, inhibited entry activity, suggesting that PRV gD may interact directly with mHveB as a ligand that can cause interference. By analogy with HSV-1, envelope-associated PRV gD probably also interacts directly with mHveB during viral entry.

scholarly journals Diverse populations of extracellular vesicles with opposite functions during herpes simplex virus 1 infection

2020 ◽  
Author(s):  
Christos Dogrammatzis ◽  
Shadia Saleh ◽  
Clayton Deighan ◽  
Maria Kalamvoki
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Extracellular Vesicles ◽  
Functional Characterization ◽  
Cell Communication ◽  
Antiviral Effect ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Extracellular vesicles (EVs) are released by all types of cells as a means of intercellular communication. Their significance lies in the fact that they can alter recipient cells functions, despite their limited capacity for cargo. We have previously demonstrated that herpes simplex virus 1 (HSV-1) infection influences the cargo and functions of EVs released by infected cells, and that these EVs negatively impact a subsequent HSV-1 infection. In the present study, we have implemented cutting-edge technologies to further characterize EVs released during HSV-1 infection. We identified distinct EV populations that were separable through a gradient approach. One population was positive for the tetraspanin CD63 and was distinct from EVs carrying components of the endosomal sorting complexes required for transport (ESCRT). Nanoparticle tracking analysis (NTA) combined with protein analysis indicated that the production of CD63+ EVs was selectively induced upon HSV-1 infection. The ExoView platform supported these data and suggested that the amount of CD63 per vesicle is higher upon infection. This platform also identified EV populations positive for other tetraspanins, including CD81 and CD9, whose abundance decreased upon HSV-1 infection. The STimulator of INterferon Genes (STING) was found in CD63+ EVs released during HSV-1 infection, while viral components were found in ESCRT+ EVs. Functional characterization of these EVs demonstrated that they have opposite effects on the infection, but the dominant effect was negative. Overall, we have identified the dominant population of EVs, and other EV populations produced during HSV-1 infection, and we have provided information about potential roles. Importance Extracellular vesicles mediate cell-to-cell communication and convey messages important for cell homeostasis. Pathways of EV biogenesis are often hijacked by pathogens to facilitate their dissemination and to establish a favorable microenvironment for the infection. We have previously shown that HSV-1 infection alters the cargo and functions of the released EVs, which negatively impact the infection. We have built upon our previous findings by developing procedures to separate EV populations from HSV-1 infected cells. We identified the major population of EVs released during infection, which carries the DNA sensor STING and has an antiviral effect. We also identified an EV population that carries selected viral proteins and has a pro-viral role. This is the first study to characterize EV populations during infection. These data indicate that the complex interactions between the virus and the host are extended to the extracellular environment and could impact HSV-1 dissemination and persistence in the host.

scholarly journals Inhibition of Herpes Simplex Virus Type 1 Infection by Cationic β-Peptides

2008 ◽  
Vol 52 (6) ◽  
pp. 2120-2129 ◽  
Author(s):  
Radeekorn Akkarawongsa ◽  
Terra B. Potocky ◽  
Emily P. English ◽  
Samuel H. Gellman ◽  
Curtis R. Brandt
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Antiviral Agents ◽  
Antiviral Effect ◽  
Helical Conformation ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Previously, it was shown that cationic α-peptides derived from the human immunodeficiency virus TAT protein transduction domain blocked herpes simplex virus type 1 (HSV-1) entry. We now show that cationic oligomers of β-amino acids (“β-peptides”) inhibit HSV-1 infection. Among three cationic β-peptides tested, the most effective inhibition was observed for the one with a strong propensity to adopt a helical conformation in which cationic and hydrophobic residues are segregated from one another (“globally amphiphilic helix”). The antiviral effect was not cell type specific. Inhibition of virus infection by the β-peptides occurred at the postattachment penetration step, with a 50% effective concentration of 3 μM for the most-effective β-peptide. The β-peptides did not inactivate virions in solution, nor did they induce resistance to infection when cells were pretreated with the β-peptides. The β-peptides showed little if any toxicity toward Vero cells. These results raise the possibility that cationic β-peptides may be useful antiviral agents for HSV-1 and demonstrate the potential of β-peptides as novel antiviral drugs.

scholarly journals The Product of the Herpes Simplex Virus 2 UL16 Gene Is Critical for the Egress of Capsids from the Nuclei of Infected Cells

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Jie Gao ◽  
Thomas J. M. Hay ◽  
Bruce W. Banfield
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sub Saharan Africa ◽  
Parental Virus ◽  
Virus Propagation ◽  
Nuclear Egress ◽  
Fold Reduction ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The herpes simplex virus (HSV) UL16 gene is conserved throughout the Herpesviridae and encodes a poorly understood tegument protein. The HSV-1 UL16 protein forms complexes with several viral proteins, including UL11, gE, VP22, and UL21. We previously demonstrated that HSV-2 UL21 was essential for virus propagation due to the failure of DNA-containing capsids (C capsids) to exit the nucleus. We hypothesized that if a UL16/UL21 complex was required for nuclear egress, HSV-2 lacking UL16 would have a phenotype similar to that of HSV-2 lacking UL21. Deletion of HSV-2 UL16 (Δ16) resulted in a 950-fold reduction in virus propagation in mouse L cell fibroblasts and a 200-fold reduction in virus propagation in Vero cells that was fully reversed upon the repair of Δ16 (Δ16R) and partially reversed by infecting UL16-expressing cells with Δ16. The kinetics of viral gene expression in cells infected with Δ16 were indistinguishable from those of cells infected with Δ16R or the parental virus. Additionally, similar numbers of capsids were isolated from the nuclei of cells infected with Δ16 and the parental virus. However, transmission electron microscopy, fluorescence in situ hybridization experiments, and fluorescent capsid localization assays all indicated a reduction in the ability of Δ16 C capsids to exit the nucleus of infected cells. Taken together, these data indicate that, like UL21, UL16 is critical for HSV-2 propagation and suggest that the UL16 and UL21 proteins may function together to facilitate the nuclear egress of capsids. IMPORTANCE HSV-2 is a highly prevalent sexually transmitted human pathogen that is the main cause of genital herpes infections and is fueling the epidemic transmission of HIV in sub-Saharan Africa. Despite important differences in the pathological features of HSV-1 and HSV-2 infections, HSV-2 is understudied compared to HSV-1. Here we demonstrate that a deletion of the HSV-2 UL16 gene results in a substantial inhibition of virus replication due to a reduction in the ability of DNA-containing capsids to exit the nucleus of infected cells. The phenotype of this UL16 mutant resembles that of an HSV-2 UL21 mutant described previously by our laboratory. Because UL16 and UL21 interact, these findings suggest that a complex containing both proteins may function together in nuclear egress.

scholarly journals Relative Contributions of Herpes Simplex Virus 1 ICP0 and vhs to Loss of Cellular IFI16 Vary in Different Human Cell Types

2016 ◽  
Vol 90 (18) ◽  
pp. 8351-8359 ◽  
Author(s):  
Megan H. Orzalli ◽  
Nicole M. Broekema ◽  
David M. Knipe
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Human Cell ◽  
Hela Cells ◽  
Viral Gene ◽  
Herpes Simplex Virus 1 ◽  
Protein Levels ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe herpes simplex virus 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase that promotes the degradation of several host cell proteins. Most studies have found that ICP0 promotes the loss of IFI16 in infected cells, but one study reported that ICP0 was not necessary or sufficient for loss of IFI16 in a tumor-derived cell line. Therefore, in this study, we examined the requirement for ICP0 in promoting the loss of IFI16 in several normal and tumor-derived cell lines. HSV-1 infection resulted in an observable decrease of IFI16 protein levels in normal human foreskin fibroblasts (HFFs), normal oral keratinocytes (NOKs), and HeLa cells but not in U2OS cells. During infection with an ICP0-null virus, we observed a reduced loss of IFI16 in HFFs and NOKs but not in HeLa cells. Ectopic expression of ICP0 from a transfected plasmid was sufficient to promote the loss of IFI16 in HFFs and NOKs. In the absence of ICP0, we observed a delayed reduction of IFI16 protein that correlated with a reduction in the steady-state levels ofIFI16mRNA. In addition, we show that the ICP0-independent loss of IFI16 in HeLa cells is dependent in part on the activity of the viral virion host shutoff (vhs) tegument protein. Together, these results demonstrate that HSV-1 promotes the loss of IFI16 through at least two mechanisms: (i) by ICP0-dependent degradation of IFI16 and (ii) by vhs-dependent turnover ofIFI16mRNA. In addition, this study highlights a potential intrinsic difference between normal and tumor-derived cells for the activities of IFI16 and HSV-1 ICP0.IMPORTANCEHSV-1 is a ubiquitous virus that establishes a lifetime persistent infection in humans. The relative success of HSV-1 as a pathogen is, in part, dependent on the expression of viral proteins that counteract host intrinsic defense mechanisms and that modulate immune responses during viral infection. In this study, we examined the relative roles of two viral gene products for the ability to promote loss of the antiviral IFI16 DNA sensor. We demonstrate that the viral immediate early ICP0 protein plays a dominant role in the loss of IFI16 in normal, but not tumor-derived, human cell lines. In contrast, viral vhs-mediated loss of IFI16 by mRNA destabilization is revealed to be dominant in tumor-derived cells in which ICP0 is nonfunctional. Together, these results contribute to our understanding of how HSV-1 modulates IFI16 protein levels and highlight cell-type-dependent differences between normal and tumor-derived cells.

scholarly journals The Antiviral Activity of Tetrachloro Decaoxide against Herpes Simplex Virus Type 1 and the Virucidal Effect of the Drug

1992 ◽  
Vol 3 (2) ◽  
pp. 95-105
Author(s):  
D. J. Dargan ◽  
J. H. Subak-Sharpe
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Antiviral Effect ◽  
Enveloped Viruses ◽  
Virucidal Effect ◽  
Simplex Virus ◽  
Hsv 1

At the recommended clinical dose for direct application to infected wounds tetrachloro decaoxide (TCDO) (1.0 × concentration TCDO) alone or in combination with haemoglobin proved to be cytotoxic for BHK and Flow 2002 cells, but at ≤0.1 TCDO/haem concentration BHK-21 cells tolerated treatment with the drug for 24 h retaining ≥80% cell viability. The in vitro cytotoxic effect is only partially reversible; but this could not explain the strong antiviral effect of TCDO/haem against herpes simplex virus type 1 (HSV-1) growing in BHK cells. The antiviral effect produces both a reduction in the number of virus particles assembled, and a lowering of their relative infectivity (i.e. reduced virus quality). The antiviral effect was active throughout the HSV-1 replication cycle. The quality of the viral DNA that was packaged into particles was unimpaired but unpackaged DNA was less infectious than controls. The reduction in particle numbers appeared to be due to both lowered protein synthesis and reduced virus particle assembly. TCDO/haem exhibits potent virucidal activity against HSV-1; HSV-2; Semliki Forest virus; Germiston virus; Reovirus type 3; Influenza virus type A; Feline leukaemia virus; Adenovirus type 5 and Polio virus type 1. Enveloped viruses, though varying over a wide sensitivity range were more sensitive than non-enveloped viruses. The magnitude of the virucidal effect against HSV-1 in suspension could be reduced by addition of BSA. The HSV-1 virucidal effect stems mainly from an effect of the drug on virion polypeptides. We propose that the effects of TCDO/haem result from the nonspecific chemical oxidation of susceptible chemical linkages both within and between individual proteins located intracellularly (antiviral and cytotoxic effects) or on the surface of virions (virucidal effect).

scholarly journals Intracellular Cre-Mediated Deletion of the Unique Packaging Signal Carried by a Herpes Simplex Virus Type 1 Recombinant and Its Relationship to the Cleavage-Packaging Process

2000 ◽  
Vol 74 (18) ◽  
pp. 8402-8412 ◽  
Author(s):  
Carine Logvinoff ◽  
Alberto L. Epstein
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Herpes Simplex Virus Type ◽  
Packaging Signal ◽  
Packaging Process ◽  
Simplex Virus ◽  
Replication Intermediates ◽  
Hsv 1

ABSTRACT To gain further insight on the function of the herpes simplex virus type 1 (HSV-1) packaging signal (a sequence), we constructed a recombinant virus containing a unique asequence, which was flanked by two loxP sites in parallel orientation. The phenotype of this recombinant, named HSV-1 LaL, was studied in cell lines which either express or do not express Cre recombinase. Although LaL virus multiplication was only slightly reduced in standard cell lines, its growth was strongly inhibited in Cre-expressing cells. In these cells, asequences were detected mostly in low-molecular-weight DNA circles, indicating that they had been excised from virus DNA by site-specific recombination. Deletion of the a sequences from the viral genome resulted in the accumulation of uncleaved replication intermediates, as observed by pulsed-field gel electrophoresis. B-type capsids also accumulated in these cells, as shown both by electron microscopy and by sucrose gradient sedimentation. Further examination of the status of asequences in Cre-expressing cells indicated that high-level amplification of this sequence can occur in the absence of the cleavage-packaging process. Moreover, the amplified asignals in small circular DNA molecules remained uncleaved, indicating that these molecules were not able to efficiently interact with the cleavage-packaging machinery. The cleavage-packaging machinery and the structural proteins required to assemble virions were, however, functional in HSV-1 LaL-infected Cre-expressing cells, since this system could be used to package plasmid DNA harboring an origin of virus replication and one normal asignal. This is the first study in which accumulation both of uncleaved replication intermediates and of B capsids has been obtained in the presence of the full set of proteins required to package virus DNA.

scholarly journals Excoecarianin, Isolated fromPhyllanthus urinariaLinnea, Inhibits Herpes Simplex Virus Type 2 Infection through Inactivation of Viral Particles

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Hua-Yew Cheng ◽  
Chien-Min Yang ◽  
Ta-Chen Lin ◽  
Liang-Tzung Lin ◽  
Lien-Chai Chiang ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Viral Entry ◽  
Herpes Simplex Virus Type ◽  
Antiviral Effect ◽  
Vero Cells ◽  
Simplex Virus ◽  
Hsv 1

Phyllanthus urinariaLinnea (Euphorbiaceae) is one of the traditional medicinal plants widely used by oriental people to treat various diseases. We have previously demonstrated that the acetone extract ofP. urinariainhibits herpes simplex virus type 2 (HSV-2) but not HSV-1 infection. In a continuing effort to clarify the antiviral mechanisms ofP. urinaria, we isolated the pure compound excoecarianin from the whole plant ofP. urinariathrough acetone extraction, and investigated its anti-HSV-1 and HSV-2 activities. Our results indicated that excoecarianin protected Vero cells from HSV-2 but not HSV-1 infection, and its 50% inhibitory concentration (IC50) was 1.4 ± 0.1 μM. The antiviral effective concentration of excoecarianin did not affect the viability or the morphology of Vero cells. Although excoecarianin inhibited HSV-2 infection, the inhibitory effect, however, was most prominent when excoecarianin was concurrently added with the virus. Pretreatment of Vero cells with excoecarianin with removal of the drug prior to infection did not yield any antiviral effects, and the same observation was made for post viral entry treatment. Subsequent studies revealed that excoecarianin inactivated HSV-2 virus particles to prevent viral infection. A synergistic antiviral effect against HSV-2 was also observed when Vero cells were treated with a combination of acyclovir (ACV) and excoecarianin. These results suggested that excoecarianin merits to be further explored as an entry inhibitor against HSV-2 and could potentially be investigated for combinatorial drug treatment with nucleoside analogues such as ACV in therapeutic management of HSV-2 infection.

Sign in / Sign up

Export Citation Format

Share Document