Host mitochondrial transcriptome response to SARS-CoV-2 in multiple cell models and clinical samples

Abstract

SARS-CoV-2 induces a muted innate immune response compared to other respiratory viruses. Mitochondrial dynamics might partially mediate this effect of SARS-CoV-2 on innate immunity. Polypeptides encoded by open reading frames of SARS-CoV and SARS-CoV-2 have been shown to localize to mitochondria and disrupt Mitochondrial Antiviral Signaling (MAVS) protein signaling. Therefore, we hypothesized that SARS-CoV-2 would distinctly regulate the mitochondrial transcriptome. We analyzed multiple publicly available RNASeq data derived from primary cells, cell lines, and clinical samples (i.e., BALF and lung). We report that SARS-CoV-2 did not dramatically regulate (1) mtDNA-encoded gene expression or (2) MAVS expression, and (3) SARS-CoV-2 downregulated nuclear-encoded mitochondrial (NEM) genes related to cellular respiration and Complex I.

ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions

“…Translation inhibition by SARS-CoV-2 Nsp1 via the blocking of mRNA access to ribosomes has been reported previously [ 61 , 62 ]. SARS-CoV-2 infection-induced down-regulation of genes associated with cellular respiration and mitochondrial function has also been shown in human lungs [ 63 ].…”

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy

“…In the case of SARS-CoV-2, it has been hypothesized that viral protein ORF9b would suppress MAVS downstream signaling (through Tumor necrosis actor Receptor-Associated Factor (TRAF)3 and TRAF6) and thereby the innate immunity and the related release of interferons could lose robustness [190]. In accordance with this prediction, it has been recently demonstrated that ORF9b from SARS-CoV-2 colocalizes on mitochondria and interacts with TOM70 protein in the outer membrane to suppresses IFN-I responses [203], and ORF9c interacts with complex I of the respiratory chain [204]. ORF9b may promote virus replication by inhibiting the apoptotic destruction of infected cells and by supporting their survival and viability through induction of mitochondrial elongation and fusion.…”

Playing Minecraft Improves Hippocampal-Associated Memory for Details in Middle Aged Adults

“…Prior research in our lab and others has demonstrated positive effects of large, immersive 3D video game playing on hippocampal-based memory ability (Clemenson and Stark, 2015 ; Clemenson et al, 2019 , 2020 ; Wais et al, 2021 ). For example, in an intervention using young non-gamer adults, we found that 2 weeks of playing Super Mario 3D World improved hippocampal-based memory performance relative to both active and no-contact control groups (Clemenson and Stark, 2015 ), with the amount of exploration in the game correlating with the amount of improvement.…”

“…The present study sought to determine whether playing Minecraft would improve memory function in middle-aged adults in the way it has improved memory function in younger adults (Clemenson et al, 2019 ) and in the way other video games centered on exploration and with large amounts of novelty have improved memory ability in both younger (Clemenson and Stark, 2015 ) and older (Clemenson et al, 2020 ; Wais et al, 2021 ) adults. The results were remarkably consistent with our prior work ( Figure 3 ) and the work of others (Wais et al, 2021 ). Even modest amounts of gameplay (e.g., 30 min/day over 2–4 weeks) improved performance on a hippocampal dependent memory task while not affecting a simpler recognition memory task that is far less reliant upon the hippocampus.…”