Host Mitochondrial Transcriptome Response to SARS-CoV-2 in Multiple Cell Models and Clinical Samples

Overview

Journal Sci Rep

Specialty Science

Date 2021 Jan 9

PMID 33420163

Citations 47

Authors

Brendan Miller

Ana Silverstein

Melanie Flores

Kevin Cao

Hiroshi Kumagai

Hemal H Mehta

Kelvin Yen

Su- Jeong Kim

Pinchas Cohen

Affiliations

Soon will be listed here.

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.

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References

Wu K, Fazal F, Parker K, Zou J, Chang H . RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus. Cell Syst. 2020; 11(1):102-108.e3. PMC: 7305881. DOI: 10.1016/j.cels.2020.06.008. View

Yoshimoto F . The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein J. 2020; 39(3):198-216. PMC: 7245191. DOI: 10.1007/s10930-020-09901-4. View

Shao H, Lan D, Duan Z, Liu Z, Min J, Zhang L . Upregulation of mitochondrial gene expression in PBMC from convalescent SARS patients. J Clin Immunol. 2006; 26(6):546-54. PMC: 7086694. DOI: 10.1007/s10875-006-9046-y. View

Jiang H, Zhang H, Meng Q, Xie J, Li Y, Chen H . SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Cell Mol Immunol. 2020; 17(9):998-1000. PMC: 7387808. DOI: 10.1038/s41423-020-0514-8. View

Lee C, Yen K, Cohen P . Humanin: a harbinger of mitochondrial-derived peptides?. Trends Endocrinol Metab. 2013; 24(5):222-8. PMC: 3641182. DOI: 10.1016/j.tem.2013.01.005. View

Mercer T, Neph S, Dinger M, Crawford J, Smith M, Shearwood A . The human mitochondrial transcriptome. Cell. 2011; 146(4):645-58. PMC: 3160626. DOI: 10.1016/j.cell.2011.06.051. View

Dhir A, Dhir S, Borowski L, Jimenez L, Teitell M, Rotig A . Mitochondrial double-stranded RNA triggers antiviral signalling in humans. Nature. 2018; 560(7717):238-242. PMC: 6570621. DOI: 10.1038/s41586-018-0363-0. View

Gordon D, Jang G, Bouhaddou M, Xu J, Obernier K, White K . A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020; 583(7816):459-468. PMC: 7431030. DOI: 10.1038/s41586-020-2286-9. View

Tiku V, Tan M, Dikic I . Mitochondrial Functions in Infection and Immunity. Trends Cell Biol. 2020; 30(4):263-275. PMC: 7126537. DOI: 10.1016/j.tcb.2020.01.006. View

10.

Riley J, Tait S . Mitochondrial DNA in inflammation and immunity. EMBO Rep. 2020; 21(4):e49799. PMC: 7132203. DOI: 10.15252/embr.201949799. View

11.

Santos J, Kowluru R . Impaired transport of mitochondrial transcription factor A (TFAM) and the metabolic memory phenomenon associated with the progression of diabetic retinopathy. Diabetes Metab Res Rev. 2012; 29(3):204-13. PMC: 3596457. DOI: 10.1002/dmrr.2384. View

12.

Yasukawa K, Oshiumi H, Takeda M, Ishihara N, Yanagi Y, Seya T . Mitofusin 2 inhibits mitochondrial antiviral signaling. Sci Signal. 2009; 2(84):ra47. DOI: 10.1126/scisignal.2000287. View

13.

Hu M, Bogoyevitch M, Jans D . Subversion of Host Cell Mitochondria by RSV to Favor Virus Production is Dependent on Inhibition of Mitochondrial Complex I and ROS Generation. Cells. 2019; 8(11). PMC: 6912631. DOI: 10.3390/cells8111417. View

14.

Yue X, Guidry J . Differential Protein Expression Profiles of Bronchoalveolar Lavage Fluid Following Lipopolysaccharide-Induced Direct and Indirect Lung Injury in Mice. Int J Mol Sci. 2019; 20(14). PMC: 6679226. DOI: 10.3390/ijms20143401. View

15.

Chong-Shan Shi , Qi H, Boularan C, Huang N, Abu-Asab M, Shelhamer J . SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J Immunol. 2014; 193(6):3080-9. PMC: 4179872. DOI: 10.4049/jimmunol.1303196. View

16.

Klompas M . Coronavirus Disease 2019 (COVID-19): Protecting Hospitals From the Invisible. Ann Intern Med. 2020; 172(9):619-620. PMC: 7081175. DOI: 10.7326/M20-0751. View

17.

Porporato P, Filigheddu N, Bravo-San Pedro J, Kroemer G, Galluzzi L . Mitochondrial metabolism and cancer. Cell Res. 2017; 28(3):265-280. PMC: 5835768. DOI: 10.1038/cr.2017.155. View

18.

Liu H, Loo Y, Horner S, Zornetzer G, Katze M, Gale Jr M . The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity. Cell Host Microbe. 2012; 11(5):528-37. PMC: 3358705. DOI: 10.1016/j.chom.2012.04.006. View

19.

Miller B, Kim S, Kumagai H, Mehta H, Xiang W, Liu J . Peptides derived from small mitochondrial open reading frames: Genomic, biological, and therapeutic implications. Exp Cell Res. 2020; 393(2):112056. PMC: 7778388. DOI: 10.1016/j.yexcr.2020.112056. View

20.

Fang R, Jiang Q, Zhou X, Wang C, Guan Y, Tao J . MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner. PLoS Pathog. 2017; 13(11):e1006720. PMC: 5699845. DOI: 10.1371/journal.ppat.1006720. View