A screening study identified decitabine as an inhibitor of Equid Herpesvirus 4 that enhances the innate antiviral response
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ABSTRACT:
PROVIDER: PRJNA1089522 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28385810.fastq.gz | Fastqsanger.gz | |||
| SRR28385811.fastq.gz | Fastqsanger.gz | |||
| SRR28385812.fastq.gz | Fastqsanger.gz | |||
| SRR28385813.fastq.gz | Fastqsanger.gz | |||
| SRR28385814.fastq.gz | Fastqsanger.gz |
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Project description:Equid herpesvirus 4 (EHV-4) is a frequent respiratory pathogen of the horse. EHV-4 sporadically induces abortion or neonatal death and although not clearly demonstrated its involvement in neurological forms is strongly suspected. Despite preventive treatments using vaccines against EHV-1/EHV-4, the resurgence of α-EHV infection still constitutes an important threat to the horse industry. Yet very few studies have been conducted on the search for antiviral molecules against EHV-4. A screening of 42 antiviral compounds was performed in vitro on E. Derm cells infected with EHV-4 405/76 reference strain (VR2230). Formation of cytopathic effects was monitored by Real-Time Cell Analysis (RTCA) and the viral load was quantified by qPCR. Aciclovir, the most widely used antiviral in vivo against alpha-herpesviruses, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for 8 molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine is the most potent compound against EHV-4 in vitro. A transcriptomic analysis revealed an increase of expression of different genes implicated in IFN response. Decitabine (DTB) seems to activate the immune antiviral pathway.
2024-06-06 | GSE261894 | GEO
Project description:Equid herpesvirus 8: complete genome sequence and association with abortion in mares
| PRJEB24126 | ENA
Project description:Identification of Equid herpesvirus 2 in tissue-engineered tendon using RNA-Sequencing
| PRJEB20552 | ENA
Project description:IntroductionEquid herpesvirus type 8 (EqHV-8) poses a significant threat to equine health, leading to miscarriages and respiratory diseases in horses and donkeys, and results in substantial economic losses in the donkey industry. Currently, there are no effective drugs or vaccines available for EqHV-8 infection control.MethodsIn this study, we investigated the in vitro and in vivo antiviral efficacy of Blebbistatin, a myosin II ATPase inhibitor, against EqHV-8.ResultsOur results demonstrated that Blebbistatin significantly inhibited EqHV-8 infection in Rabbit kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cells in a concentration-dependent manner. Notably, Blebbistatin was found to disrupt EqHV-8 infection at the entry stage by modulating myosin II ATPase activity. Moreover, in vivo experiments revealed that Blebbistatin effectively reduced EqHV-8 replication and mitigated lung pathology in a mouse model.ConclusionCollectively, these findings suggest that Blebbistatin holds considerable potential as an antiviral agent for the control of EqHV-8 infection, presenting a novel approach to addressing this veterinary challenge.
| S-EPMC11186319 | biostudies-literature
Project description:Equid gammaherpesvirus 2 Raw sequence reads
| PRJNA858451 | ENA
Project description:Equid alphaherpesvirus 8 Raw sequence reads
| PRJNA787358 | ENA
Project description:Highly efficacious antiviral protection of plants by siRNAs identified in vitro
| PRJNA497995 | ENA
Project description:Dysregulation of DNA methylation is an established feature of breast cancers. DNA demethylating therapies like decitabine are proposed for the treatment of triple-negative breast cancers (TNBCs) and indicators of response need to be identified. For this purpose, we characterized the effects of decitabine in a panel of 10 breast cancer cell lines and observed a range of sensitivity to decitabine that was not subtype-specific. Knockdown of potential key effectors demonstrated the requirement of deoxycytidine kinase (DCK) for decitabine response in breast cancer cells. In treatment-naive breast tumors, DCK was higher in TNBCs, and DCK levels were sustained or increased post chemotherapy treatment. This suggests that limited DCK levels will not be a barrier to response in TNBC patients treated with decitabine as a second line treatment or in a clinical trial. Methylome analysis revealed that genome-wide, region-specific, tumor suppressor gene-specific methylation, and decitabine-induced demethylation did not predict response to decitabine. Gene set enrichment analysis (GSEA) of transcriptome data demonstrated that decitabine induced genes within apoptosis, cell cycle, stress, and immune pathways in decitabine treated cells. Induced genes included those characterized by the viral mimicry response; however knockdown of key effectors of the pathway did not affect decitabine sensitivity suggesting that breast cancer growth suppression by decitabine is independent of viral mimicry. Finally, taxol-resistant breast cancer cells expressing high levels of multidrug resistance transporter ABCB1 remained sensitive to decitabine, suggesting that the drug could be used as second-line treatment for chemoresistant patients. We used microarrays to determine genome-wide expression changes induced by DNA de-methylating agent decitabine in breast cancer cell lines
2020-06-01 | GSE133987 | GEO
Project description:Equid herpesvirus type 1 (EHV-1) causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression) and platelet microvesiculation (increased small events double positive for CD41 and Annexin V). Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM). A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis that occurs in clinically infected horses and provides a new mechanism by which viruses activate hemostasis.
| S-EPMC4407896 | biostudies-literature