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ABSTRACT: Sequencing of VEEV TC-83 genomes in the presence of BDGR-49

PROVIDER: PRJNA947109 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23928182_1.fastq.gz	Fastqsanger.gz
	SRR23928182_2.fastq.gz	Fastqsanger.gz
	SRR23928183_1.fastq.gz	Fastqsanger.gz
	SRR23928183_2.fastq.gz	Fastqsanger.gz
	SRR23928184_1.fastq.gz	Fastqsanger.gz

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Project description:Sequencing of VEEV TC-83 genomes in the presence of BDGR-164

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Analysis of VEEV Capsid Interaction Sites

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

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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.

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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.

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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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2024-05-21 | PXD044305 | Pride

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Project description:Testicular cancer (TC) is the most common solid tumour in young men. While cisplatin-based chemotherapy is highly effective in TC patients, chemoresistance still accounts for 10% of disease-related deaths. Pre-clinical models that faithfully reflect patient tumours are needed to assist in target discovery and drug development. Tumour pieces from eight TC patients were subcutaneously implanted in NOD scid gamma (NSG) mice. Three patient-derived xenograft (PDX) models of TC, including one chemoresistant model, were established containing yolk sac tumour and teratoma components. Whole-exome sequencing, copy number variation analysis and RNA-sequencing was performed on these TP53 wild type PDX tumours to assess the effects of passaging, showing high concordance of molecular features between passages.

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Isolation and whole protein characterization of species A and B bovine rotaviruses from Chinese calves.

Project description:Rotaviruses (RVs) account for severe diarrhea in children and young animals globally. In the current study, the fecal samples of diarrheic calves from a beef farm in Inner Mongolia were screened for RVA by ELISA and RT- PCR, followed by culture of three positive RVA samples in the MA-104 cell line. After 10 blind passages, cytopathic effects (CPE) appeared as detachment, granulation, and clustering of the inoculated cells. The virus isolates were identified by RT-PCR (VP6 gene RVA) and ESI-LC-MS/MS for whole protein sequencing. The protein sequences demonstrated the presence of two strains from species A rotavirus and one RVB strain; RVA/Cow-tc/ CHN/35333/2019/G6P[5] was mixed with one RVB strain (RVB/Cow-tc/CHN/35334/2019/G5P[3]) in two samples, and RVA/Cow-tc/CHN/10927/2019/G8P[7] was found in one sample. They are of genotype constellations (G6-P[5]-I2-R2-C2-M2-A3-N2-T6-E2-H3), (G8-P[7]-I5-R1-C1- M2-A1-N1-T1-E1-H1), and (G5-P[3]-I3-R5- C5-A5-N4-H5), respectively. Besides, phylogenetic analysis of the obtained sequences demonstrated viral evolution.

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