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SARS-CoV-2 infection unevenly impacts metabolism in the coronal periphery of the lungs

ABSTRACT: This project was performed on a cohort of mice that were either infected on day 5 with 1000 or 5000 pfu (D5_1000 or D5_5000), uninfected on day 5 (D5_MOCK), infected on day 20 (D20) or uninfected on day 20 (D20_MOCK). Lungs were removed and broken into 12 pieces. See "SARS-CoV-2 infection unevenly impacts metabolism in the coronal periphery of the lungs" for more information on this study

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Laura-Isobel McCall

PROVIDER: MSV000094591 | MassIVE | Mon Apr 22 08:31:00 BST 2024

REPOSITORIES: MassIVE

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Project description:For the purpose of establishing a mice model for sever COVID-19 , mice were infected intranasally with SARS-CoV-2 two days after pulmonary application of low-dose ricin. The goal of this study is to perform a comparative transcriptomic analysis by exploring the alterations in gene expression in lungs of mice exposed to low-dose ricin and SARS-CoV-2 (samples OR009-OR012) compared to lungs of mice infected solely with SARS-CoV-2 (48 hr after infection, samples OR021-OR024) or mice exposed to low-dose ricin (96 hr post exposure,samples OR005-OR008)) or mice exposed to lethal dose of ricin (48 hr post exposure, samples OR013-OR016). Methods: Total RNA was extracted from lungs of ricin intoxicated mice (intranasally exposure to 1.7 µg/kg or 10 µg/kg ricin ) or of SARS-CoV-2 infected mice (intranasal administration of 5 x 106 PFU), using the RNeasy mini kit (Qiagen). RNA-seq libraries were constructed and sequencing of 100bp paired-end was performed on the Illumina NovaSeq 6000 system. Sequencing yielded about 22M reads per sample that were mapped to the mouse genome. RNA ratios were clustered using partitioning clustering. We next carried out Ingenuity Pathway Analysis (IPA). Results: Principal component analysis revealed distinct transcriptional signatures between lungs mice exposed to low-dose ricin and infected with SARS-CoV-2 compared to lungs of mice infected solely with SARS-CoV-2 or mice exposed to low-dose ricin (96 hr post exposure) or mice exposed to lethal dose of ricin (48 hr post exposure). Differentially Expressed Genes (DEGs) were defined as such when having false discovery rate (FDR) value (p-adjusted) of ≤ 0.01 and a fold change (FC) of ≥ 1.5 or ≤ 0.66. Analysis of Low-dose-ricin-treated mice transcripts resulted in the detection of 6684 DEGs, 55% upregulated and 45% downregulated. Similarly, in Low-dose-ricin-treated mice infected with SARS-CoV-2, we found a total of 6044 differentially expressed genes, 52% induced and 48% repressed. Considerably fewer (797, 67% upregulated and 33% downregulated) differentially expressed genes were identified in lungs of mice infected only with SARS-CoV-2.

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SARS-CoV-2 infection unevenly impacts metabolism in the coronal periphery of the lungs

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