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Investigating cellular transcriptomic alterations caused by VEEV replicase and SARS-CoV-2 mRNA co-transfection

ABSTRACT: Investigating cellular transcriptomic alterations caused by VEEV replicase and SARS-CoV-2 mRNA co-transfection

PROVIDER: PRJNA1164791 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30786702.fastq.gz	Fastqsanger.gz
	SRR30786703.fastq.gz	Fastqsanger.gz
	SRR30786704.fastq.gz	Fastqsanger.gz
	SRR30786705.fastq.gz	Fastqsanger.gz
	SRR30786706.fastq.gz	Fastqsanger.gz

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Investigating cellular transcriptomic alterations caused by VEEV replicase and SARS-CoV-2 mRNA co-transfection

Project description:The viral RNA-dependent RNA polymerase (replicase) from Venezuelan equine encephalitis virus constitutes a vital component of the bipartite trans-amplifying mRNA vaccine. In this vaccine strategy aimed at targeting SARS-CoV-2, the replicase mRNA is administered alongside the mRNA encoding the SARS-CoV-2 spike protein. Our investigation sought to determine whether the replicase induces amplification of cellular mRNAs. To this end, cells were transfected with mRNAs encoding the replicase and SARS-CoV-2 spike protein, while control groups received transfections of mRNAs encoding an unrelated protein along with the SARS-CoV-2 spike. We observed no significant upregulation of genes in the treatment group compared to the control group. This suggests that the replicase does not induce off-target amplification of cellular mRNAs.

2024-10-07 | GSE277947 | 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.

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Analysis of VEEV Capsid Interaction Sites

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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

Spatial Transcriptomics of Brains Infected with VEEV

Project description:Spatial Transcriptomics of Brains Infected with VEEV

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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

TI caused by SARS-CoV-2

Project description:TI caused by SARS-CoV-2

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

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

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