Similar Datasets
Project description:Analysis of VEEV Capsid Interaction Sites
| PRJNA545986 | ENA
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
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
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
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 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.
2026-03-30 | GSE324524 | GEO
Project description:Comparison of multiple passages of VEEV V4020 to VEEV TC-83 at 2 days after intracranial inoculation in BALB/c mice
| PRJNA596646 | ENA
Project description:Suboptimal prophylactic treatments with BDGR-49 in a lethal VEEV TC-83 mouse model
| PRJNA1162158 | ENA
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
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