Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of host lncRNAs that impact Venezuelan equine encephalitis virus replication

ABSTRACT: Venezuelan equine encephalitis virus (VEEV) causes encephalitis in humans and equids, and there are no vaccines or therapeutics available for humans. In recent years, non-coding RNAs have emerged as critical regulatory factors affecting different cellular pathways. Specifically, long non-coding RNAs (lncRNAs) have been identified as regulators of antiviral pathways during various viral infections; however, their role in regulating VEEV infection has not been assessed. Here we show differential expression of several lncRNAs in primary mouse target cells infected with a vaccine strain of VEEV (TC-83) but not a pathogenic strain (TrD). Among the differentially expressed genes (DEGs), suppressing lncRNA small nucleolar RNA host gene 15 (Snhg15) resulted in about a 7-fold increase in VEEV TC-83 replication in primary mouse a strocytes. Knockdown of Snhg15 during VEEV TC-83 infection resulted in thesuppression of ten genes including Irf1, Junb, Atf3, Relb, Pim1, Hbegf, Ccl5, Ankrd33b, and H2-K2, all of which were also increased during TC-83 infection when the expression of Snhg15 increased in primary mouse astrocytes. Most of these genes are involved inantiviral responses. KEGG pathway analysis confirmed the suppression of both pattern recognition receptor and inflammatory pathways after in Snhg15 knockdown. These data are the first to identify lncRNA responses in encephalitic alphavirus infection and demonstrate important roles for these overlooked RNAs on VEEV infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE324524 | GEO | 2026/03/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of host lncRNAs that impact Venezuelan equine encephalitis virus replication

Project description:Venezuelan equine encephalitis virus (VEEV) causes encephalitis in humans and equids, and there are no vaccines or therapeutics available for humans. In recent years, non-coding RNAs have emerged as critical regulatory factors affecting different cellular pathways. Specifically, long non-coding RNAs (lncRNAs) have been identified as regulators of antiviral pathways during various viral infections; however, their role in regulating VEEV infection has not been assessed. Here we show differential expression of several lncRNAs in primary mouse target cells infected with a vaccine strain of VEEV (TC-83) but not a pathogenic strain (TrD). Among the differentially expressed genes (DEGs), suppressing lncRNA small nucleolar RNA host gene 15 (Snhg15) resulted in about a 7-fold increase in VEEV TC-83 replication in primary mouse astrocytes. Knockdown of Snhg15 during VEEV TC-83 infection resulted in the suppression of ten genes including Irf1, Junb, Atf3, Relb, Pim1, Hbegf, Ccl5, Ankrd33b, and H2-K2, all of which were also increased during TC-83 infection when the expression of Snhg15 increased in primary mouse astrocytes. Most of these genes are involved in antiviral responses. KEGG pathway analysis confirmed the suppression of both pattern recognition receptor and inflammatory pathways after in Snhg15 knockdown. These data are the first to identify lncRNA responses in encephalitic alphavirus infection and demonstrate important roles for these overlooked RNAs on VEEV infection.

2026-03-30 | GSE324479 | GEO

Suboptimal prophylactic treatments with BDGR-49 in a lethal VEEV TC-83 mouse model

Project description:To study emergence of resistance to BDGR-49 during infection with Venezuelan equine encephalitis virus (VEEV), mice were treated suboptimal treatment regimen. C3H/HeN mice were prophylactically treated with BDGR-49 2 hours prior to infection for a total of 5 days. Mice were infected with a lethal challenge dose of VEEV TC-83. Following infection mice brains were euthanized on 3-, 5-, 7,9-, and 10-days post-infection and their brains collected and RNA-Seq performed on. RNA-Seq results were used to analyze for viral resistant mutants. Analysis revealed that only one of the mice contained a mutant that is potentially resistant to BDGR-49.

2025-01-06 | GSE277431 | GEO

Hippocampal single cell transcriptomic changes and cellular remodeling is associated with chronic neurobehavioral outcomes following alphavirus infection

Project description:Viral infections, including Venezuelan equine encephalitis virus (VEEV), have been likened to neurological diseases such as Parkinson’s and Alzheimer’s, though mechanisms remain unclear. VEEV, a neuroinvasive alphavirus, can cause significant neurological deficits in humans. Chronic effects of VEEV are poorly understood, with no antivirals or neuroprotective treatments available. This study examines longitudinal neuropathological, behavioral, and single-cell transcriptomic changes in C57BL/6 mice intranasally infected with VEEV TC-83. Acute infection significantly altered inflammatory and innate immune signaling and induced astrocyte and microglia activation and loss of neurons in the hippocampus. Persistent motor dysfunction, memory impairment, and reduced anxiety-like behavior were observed up to 106 days post-infection (DPI). These changes correlated with alterations in synaptogenic signaling gene expression, neuron loss, and persistent glia cell activation at 106 DPI. Collectively, this study demonstrates that infection with VEEV induces chronic alterations in the hippocampus that may correlate with neurological sequalae observed in human patients.

2026-03-23 | GSE289596 | GEO

Analysis of VEEV Capsid Interaction Sites

Project description:Brief assessment of VEEV TC-83 Capsid:RNA interactions.

2020-05-25 | GSE132125 | GEO

Deep Spatial Profiling of Venezuelan Equine Encephalitis Virus Reveals Increased Genetic Diversity Amidst Neuroinflammation and Cell Death During Brain Infection

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

Broad spectrum efficacy of BDGR-164 against neurotropic alphaviruses and correlates of protection

Project description:Infections by the New World alphaviruses, Eastern Equine encephalitis virus (EEEV), Venezuelan Equine encephalitis virus (VEEV), and Western Equine encephalitis virus (WEEV), cause febrile illness that can progress to fatal disease in humans and equids. Currently there are no FDA-approved antivirals for prophylactic or therapeutic treatment of human infection by these viruses. To combat these infections, we have developed a novel small molecule, BDGR-164, which has subnanomolar potency against VEEV, EEEV, and WEEV. Using an intranasal route of virus infection in a lethal BALB/c model, prophylactic subcutaneous administration of BDGR-164 conferred 100% (VEEV), 88% (EEEV), and 63% (WEEV) survival. To evaluate the ability of BDGR-164 to reduce viral RNA/antigen, inflammation, and pathogenesis, we used RNASeq and histopathology of whole brain at 4 days post-infection (dpi). Viral RNA levels and antigen were reduced significantly in virus-infected and BDGR-164-treated versus virus-infected, sham-treated mice. Moreover, there was a significant reduction in host immune responses associated with inflammatory signaling, immune cell recruitment, and programmed cell death in virus-infected, BDGR-164 treated mice. Cytokine analyses of sera corroborated the reduction in upregulation of the immune response in virus-infected, BDGR-164 treated mice. Limited antiviral resistance to BDGR-164 was detected in one mouse on 4 dpi at NSP2:Y102C. In conclusion, our studies suggest that BDGR-164 has broad and potent prophylactic efficacy against the neurotropic alphaviruses.

2025-01-06 | GSE255795 | GEO

Comparison of multiple passages of VEEV V4020 to VEEV TC-83 at 2 days after intracranial inoculation in BALB/c mice

Project description:Experimental V4020 is derived from VEEV TC-83, a vaccine with a long track record of use in lab and military personnel at risk. V4020 was generated from an infectious DNA clone, secured genetic stability by employing stabilizing mutation at position 120 in the E2 protein, and by rearrangement of structural genes. In this study, serial passages in brain tissues of mice were performed to compare safety and genetic stability of V4020 and TC-83 experimental vaccines. During five serial passages in brain, less severe clinical manifestations and lower viral load were observed in V4020 mice and all animals survived. In contrast, 13.3% of mice met euthanasia criteria during the passages in TC-83 group. At 2 DPI, RNA-Seq analysis of brain tissues revealed that V4020 mice had lower rates of mutations throughout five passages. Higher synonymous mutation ratio was observed in the nsP4 (RdRP) gene of TC-83 compared to V4020 mice. At 2 DPI, both viruses induced different expression profiles of host genes involved into neuro-regeneration. Taken together, these results provide evidence for the improved safety and genetic stability of the experimental V4020 VEEV vaccine in a murine model. While no single nucleotide polymorphisms that have been previously linked to virulence were identified, more neuro-virulence markers were observed in serial passaged TC-83 compared to V4020. This study suggests a complex polygenic basis for neuro-virulent reversion in VEEV live attenuated vaccines and provides evidence for the advanced safety and genetic stability of V4020.

2020-06-01 | GSE142325 | GEO

The lipopeptide Pam3CSK4 inhibits Rift Valley fever virus infection and protects from encephalitis

Project description:Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections.

2024-06-18 | GSE241547 | GEO

Spatial Transcriptomics of Brains Infected with VEEV

Project description:Venezuelan equine encephalitis virus (VEEV) is a neurotropic alphavirus that causes neurological disease in both humans and equine. In this study we paired spatial transcriptomics and a mouse model of VEEV to generate a transcriptomic profile of infected or control brains at 6 days post infection. We identified regionally distinct myeloid and lymphocyte populations, contributing to our understanding of the neuroinflammation caused by VEEV.

2024-12-09 | GSE275201 | GEO

Single-cell transcriptomic profiling of brain immune infiltration following Venezuelan equine encephalitis virus infection

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data