SARS-CoV-2 induces a unique mitochondrial transcriptome signature

Abstract SARS-CoV-2 has challenged global healthcare systems in part because its clinical manifestations are heterogeneous. Variable symptoms of SARS-CoV-2 could be attributed to the virus’ ability to mildly induce an innate immune response, as prior transcriptomic data has suggested. Mitochondrial dynamics might partially mediate the effect of SARS-CoV-2 on innate immunity. Many proteins encoded by SARS-CoV have been shown to localize to mitochondria and inhibit Mitochondrial Antiviral Signaling protein (MAVS). We analyzed multiple publicly available RNASeq data in order to unravel the metabolic and mitochondrial transcriptome signature of SARS-CoV-2 in primary cells, cell lines, and clinical samples (i.e., BALF and lung). We report here that SARS-CoV-2 does not dramatically regulate (1) mitochondrial-gene expression or (2) MAVS expression, but (3) downregulates nuclear-encoded mitochondrial (NEM) genes related to cellular respiration and Complex 1 assembly. We also report cell-specific and tissue-specific effects of SARS-CoV-2 on the mitochondrial-encoded and NEM transcriptome that could inform future experimental paradigm selection.