Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Joseph W. Guarnieri; Joseph M. Dybas; Hossein Fazelinia; Man Soo Kim; Justin J. Frere; Yuanchao Zhang; Yentli E. Soto Albrecht; Deborah G. Murdock; Alessia Angelin; Larry N. Singh; Scott L. Weiss; Sonja M. Best; Marie T. Lott; Henry Cope; Victoria Zaksas; Amanda Saravia-Butler; Cem Meydan; Jonathan Foox; Christopher Mozsary; Yared H. Kidane; Waldemar Priebe; Mark R. Emmett; Robert Meller; Urminder Singh; Yaron Bram; Benjamin Robert tenOever; Mark T. Heise; Nathaniel J. Moorman; Emily A. Madden; Sharon Taft-Benz

doi:10.1101/2022.02.19.481089

Molecular BiologybioRxivFeb 19, 2022

Preprint

Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Joseph W. Guarnieri iD, Joseph M. Dybas iD, Hossein Fazelinia iD, Man Soo Kim iD, Justin J. Frere iD, Yuanchao Zhang iD, Yentli E. Soto Albrecht iD, Deborah G. Murdock iD, Alessia Angelin iD, Larry N. Singh iD, Scott L. Weiss iD, Sonja M. Best iD, Marie T. Lott iD, Henry Cope iD, Victoria Zaksas iD, Amanda Saravia-Butler iD, Cem Meydan iD, Jonathan Foox iD, Christopher Mozsary iD, Yared H. Kidane, Waldemar Priebe iD, Mark R. Emmett iD, Robert Meller iD, Urminder Singh iD, Yaron Bram iD, , Douglas C. Wallace iD

Abstract

Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported in COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal the dynamics of COVID-19 through transcription profiles in nasopharyngeal and autopsy samples from patients and infected rodent models. While mitochondrial bioenergetics is repressed in the viral nasopharyngeal portal of entry, it is up regulated in autopsy lung tissues from deceased patients. In most disease stages and organs, discrete OXPHOS functions are blocked by the virus, and this is countered by the host broadly up regulating unblocked OXPHOS functions. No such rebound is seen in autopsy heart, results in severe repression of genes across all OXPHOS modules. Hence, targeted enhancement of mitochondrial gene expression may mitigate the pathogenesis of COVID-19. One-Sentence SummaryCovid-19 is associated with targeted inhibition of mitochondrial gene transcription.

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