Venezuelan equine encephalitis virus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA157941 | ENA |
REPOSITORIES: ENA
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Project description:No vaccines or antivirals are approved against Venezuelan equine encephalitis virus (VEEV) infection in humans. To improve our understanding of VEEV-host interactions, we simultaneously profiled host transcriptome and viral RNA (vRNA) in thousands of single cells during infection of human astrocytes. Host transcription was suppressed, and “superproducer cells” with extreme vRNA abundance and altered transcriptome emerged during the first viral life cycle. Cells with increased structural-to-nonstructural transcript ratio demonstrated upregulation of trafficking genes at later time points. Loss- and gain-of-function experiments confirmed pro- and antiviral host factors. Single-cell deep sequencing analysis identified a viral E3 protein mutation altering host gene expression. Lastly, comparison with data from other viruses highlighted common and unique pathways perturbed by infection across evolutionary scales. This study provides a high-resolution characterization of the cellular response to VEEV infection, identifies candidate targets for antivirals, and establishes a comparative single-cell approach to study the evolution of virus-host interactions.
2020-02-25 | GSE145815 | GEO
Project description:We performed whole genome single nucleotide polymorphism (SNP) based analysis of all available Venezuelan equine encephalitis (VEE) virus antigenic complex genomes and developed a high resolution genome-wide SNP microarray. We used the SNP microarray to analyze a broad panel of VEEV isolates, found excellent concordance between array and sequence based genotypes for previously sequenced strains, and genotyped unsequenced strains.
2016-03-24 | GSE79530 | GEO
Project description:Venezuelan equine encephalitis virus Genome sequencing
| PRJNA438670 | ENA
Project description:Neurotropic alphaviruses such as Venezuelan equine encephalitis virus (VEEV) are critical human pathogens that continually expand to naïve populations and for which there are no licensed vaccines or therapeutics. The neuropathology of VEEV has been attributed to the immune response in the brain yet the underlying mechanisms and specific immune cell populations involved are not fully elucidated. In this study, a murine model of lethal VEEV infection is paired with single-cell RNA sequencing to transcriptionally profile the immune response longitudinally in the brain following infection. Infection-induced immune changes in the brain was also compared to changes in peripheral blood mononuclear cells (PBMCs). The results define an inflammatory response involving transcriptionally distinct subpopulations of activated microglia and infiltrating proinflammatory myeloid populations and cytotoxic lymphocytes. This study advances our understanding of the immune mechanisms underlying viral encephalitis toward the goal of identifying new therapeutic targets.
2024-12-09 | GSE274566 | GEO
Project description:Venezuelan, Western and Eastern Equine Encephalitis Virus (VEEV, WEEV and EEEV), genus Alphavirus, causes a febrile illness that may result in fatal neurological disease which has no FDA-approved antivirals for the prevention or treatment. To address this gap, we developed a novel brain-penetrant, small molecule, BDGR-49, which when administered subcutaneously at 6 mg/kg twice per day for 6 days conferred 100% protection against a lethal intranasal challenge of VEEV Trinidad donkey (TrD) in BALB/c mouse model. By eight days post-infection (dpi), viral load in the brain of BDGR-49-treated mice was significantly reduced whereas TrD-infected, sham-treated mice succumbed to disease on 5 dpi. Analysis of the host responses in the brains of VEEV TrD-infected, BDGR-49-treated, mice resulted in a significant reduction in expression of genes in pathways associated with inflammation and cell death.
2025-01-06 | GSE277300 | GEO
Project description:Differing from other experimental models, intranasal infection with vaccine strain of Venezuelan equine encephalitis virus, VEEV, (TC83) caused high titer infection in the brain and 90–100% mortality in the C3H/HeN murine model. Intranasal infection with VEEV (TC83) caused persistent viral infection in the brains of mice without functional αβ T-cells (αβ-TCR -/-). While wild-type C57BL/6 mice clear infectious virus in the brain by 13 dpi, αβ-TCR -/- maintain infectious virus in the brain to 92 dpi. To better characterize the susceptibility to disease development in different strains of mice, we have analyzed the gene transcriptomes in the brains of infected mice.
2016-12-10 | GSE91074 | GEO
Project description:The innate immune protection provided by cationic antimicrobial peptides (CAMPs) has been shown to extend to antiviral activity, with putative mechanisms of action including direct interaction with host cells or pathogen membranes. The lack of therapeutics available for the treatment of viruses such as Venezuelan equine encephalitis virus (VEEV) underscores the urgency of novel strategies for antiviral discovery. American alligator plasma has been shown to exhibit strong in vitro antibacterial activity, and functionalized hydrogel particles have been successfully employed for the identification of specific CAMPs from alligator plasma. Here, a novel bait strategy in which particles were encapsulated in membranes from either healthy or VEEV-infected cells was implemented to identify peptides preferentially targeting infected cells for subsequent evaluation of antiviral activity. Statistical analysis of peptide identification results was used to select five candidate peptides for testing, of which three exhibited a dose-dependent inhibition of VEEV, with one peptide also significantly inhibiting infectious titers. Results suggest our bioprospecting strategy provides a versatile platform that may be adapted for antiviral peptide identification from complex biological samples.
2022-05-27 | MSV000089560 | MassIVE
Project description:The high mutation rate of RNA viruses provides viral populations with the ability to adapt to new environments but also makes them vulnerable to extinction due to the deleterious effects of mutations, which is the conceptual basis for the antiviral activity of RNA mutagens. However, there are still gaps in the quantitative understanding of the dynamics between the mutations induced by an RNA mutagen and its effects on viral fitness. To address this, we used Venezuelan Equine Encephalitis Virus (VEEV) and the potent RNA mutagen β-d-N4-hydroxycytidine (NHC) as a model to analyze virus replication competency and mutation frequency following treatment in the total and replication-competent viral populations separately. We found that NHC induced transition mutations in a concentration dependent manner in the total population, while the replication-competent population maintained itself within an increased, yet narrow, mutation spectrum. The incorporation of NHC mainly happened during the positive sense RNA synthesis of VEEV. A growth kinetic analysis of VEEV population treated with NHC pointed to a lower but more diverse distribution in mutational fitness, demonstrating that NHC-induced mutations negatively and broadly affect the fitness of the virus. Together, our study provides mechanistic insight into how RNA mutagens affect viral population landscape and the potential of RNA mutagens as an antiviral strategy for alphaviruses.
2024-10-25 | GSE207136 | GEO
Project description:Characterization of genetic variability of Venezuelan equine encephalitis viruses
| PRJNA316099 | ENA
Project description:Venezuelan equine encephalitis virus (VEEV) causes a febrile illness that can progress to neurological disease with the possibility of death in human cases. The evaluation and optimization of therapeutics that target brain infections demands knowledge of the host’s response to VEEV, the dynamics of infection, and the potential for within-host evolution of the virus. We hypothesized that selective pressures during infection of the brain may differ temporally and spatially and so we investigated the dynamics of the host response, viral transcript levels, and genetic variation of VEEV TC-83 in eight areas of the brain in mice over 7 days post-infection (dpi). Viral replication increased throughout the brain until 5-6 dpi and decreased thereafter with neurons as the main site of viral replication. Low levels of genetic diversity were noted on 1 dpi, and was followed by an expansion in the genetic diversity of VEEV and nonsynonymous mutations (Ns) that peaked by 5 dpi. The proinflammatory response and the influx of immune cells mirrored the levels of virus and correlated with substantial damage to neurons by 5 dpi and increased activation of microglial cells and astrocytes. The prevalence and dynamics of Ns mutations suggests that the VEEV is under selection within the brain and that progressive neuroinflammation may play a role in acting as a selective pressure.
2023-07-21 | GSE213725 | GEO