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Series GSE142325 Query DataSets for GSE142325
Status Public on Jun 01, 2020
Title Comparison of multiple passages of VEEV V4020 to VEEV TC-83 at 2 days after intracranial inoculation in BALB/c mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design RNA isolated from brain tissue of VEEV V4020 or VEEV TC-83 mice 2 days following intracranial inoculation of five serial passages was sequenced. Two replicates of each sample were included except for V4020 passage 1, and TC-83 passages 2, 3, 4, and 5 which were each a single sample.
 
Contributor(s) Johnson DM, Sokoloski KJ, Jokinen JD, Pfeffer TL, Chu Y, Adcock RS, Chung D, Tretyakova I, Pushko P, Lukashevich IS
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Submission date Dec 19, 2019
Last update date Jun 01, 2020
Contact name Dylan MacGregor Johnson
E-mail(s) dylan.johnson@louisville.edu
Phone 5028525394
Organization name University of Louisville, School of Medicine
Department Microbiology & Immunology
Lab Lab of Igor S. Lukashevich
Street address 505 S Hancock St., CTRB RM642B
City Louisville
State/province KY
ZIP/Postal code 40202
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (15)
GSM4225295 2-V4020-P1
GSM4225296 31-V4020-P2
GSM4225297 32-V4020-P2
Relations
BioProject PRJNA596646
SRA SRP238205

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Supplementary file Size Download File type/resource
GSE142325_VEEV_V4020_and_TC-83_variant_analysis.xlsx 62.8 Mb (ftp)(http) XLSX
GSE142325_mm10_aligned_DESeq2.xlsx 31.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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