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HGNC Genes

SARS-CoV-2 proteins

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    Network Analysis and Transcriptome Profiling Identify Autophagic and Mitochondrial Dysfunctions in SARS-CoV-2 Infection MESHD

    Authors: Komudi Singh; Yun-Ching Chen; Jennifer T. Judy; Fayaz Seifuddin; Ilker Tunc; Mehdi Pirooznia

    doi:10.1101/2020.05.13.092536 Date: 2020-05-14 Source: bioRxiv

    Analyzing host transcriptional changes in response to SARS-CoV-2 infection MESHD will help delineate biological processes underlying viral pathogenesis. Comparison of expression profiles of lung cell lines A549 (infected with either SARS-CoV-2 (with ACE2 expression)) or Influenza A virus (IAV)) and Calu3 (infected with SARS-CoV-2 or MERS-CoV) revealed upregulation of the antiviral interferon signaling in all three viral infections. However, perturbations in inflammatory, mitochondrial, and autophagy processes were specifically observed in SARS-CoV-2 infected MESHD cells. Validation of findings from cell line data revealed perturbations in autophagy and mitochondrial processes in the infected human nasopharyngeal samples. Specifically, downregulation of mTOR HGNC expression, mitochondrial ribosomal, mitochondrial complex I, and lysosome acidification genes were concurrently observed in both infected cell lines and human datasets. Furthermore, SARS-CoV-2 infection MESHD impedes autophagic flux by upregulating GSK3B HGNC in lung cell lines, or by downregulating autophagy genes, SNAP29 HGNC and lysosome acidification genes in human samples, contributing to increased viral replication. Therefore, drugs targeting lysosome acidification or autophagic flux could be tested as intervention strategies. Additionally, downregulation of MTFP1 HGNC (in cell lines) or SOCS6 HGNC (in human samples) results in hyperfused mitochondria and impede proper interferon response. Coexpression networks analysis identifies correlated clusters of genes annotated to inflammation MESHD and mitochondrial processes that are misregulated in SARS-CoV-2 infected MESHD cells. Finally, comparison of age stratified human gene expression data revealed impaired upregulation of chemokines, interferon stimulated and tripartite motif genes that are critical for antiviral signaling. Together, this analysis has revealed specific aspects of autophagic and mitochondrial function that are uniquely perturbed in SARS-CoV-2 infection MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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