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

BioRxiv : the Preprint Server for Biology
Komudi SinghMehdi Pirooznia

Abstract

Analyzing host transcriptional changes in response to SARS-CoV-2 infection 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 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 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 impedes autophagic flux by upregulating GSK3B in lung cell lines, or by downregulating autophagy genes, SNAP29 and lysosome acidification genes in human samples, contributing to increased viral replication. Therefore, drugs targeting lysosome acidification or autophagic flux could be te...Continue Reading

Citations

Aug 9, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Santosh Shenoy
Jan 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Leonardo LupacchiniPatrizia Russo
Jan 13, 2021·Briefings in Bioinformatics·Md Asif AhsanMing Chen
Apr 30, 2021·Frontiers in Neurology·Mar Pacheco-HerreroJosé Luna-Muñoz
May 26, 2021·NPJ Systems Biology and Applications·Marisol Salgado-AlbarránErnesto Soto-Reyes
Aug 12, 2021·International Reviews of Immunology·Nada J HabeichiFouad A Zouein

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Datasets Mentioned

BETA
GSE147507
GSE139516

Methods Mentioned

BETA
RNA seq
sc
transfection
GTPase
biopsy
RNA
RNA-seq
scRNA seq

Clinical Trials Mentioned

NCT04322773

Software Mentioned

Seurat
WGCNA
voom
Cytoscape
Synapse
Enrichment Map
R
clusterProfiler
GeneMANIA
AutoAnnotate

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