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

Guarnieri, J. W.; Dybas, J. M.; Fazelinia, H.; Kim, M. S.; Frere, J.; Zhang, Y.; Albrecht, Y. S.; Murdock, D. G.; Angelin, A.; Singh, L. N.; Weiss, S. L.; Best, S. M.; Lott, M. T.; Cope, H.; Zaksas, V.; Saravia-Butler, A.; Meydan, C.; Foox, J.; Mozsary, C.; Kidane, Y. H.; Priebe, W.; Emmett, M.; Meller, R.; Singh, U.; Bram, Y.; tenOever, B. R.; Heise, M. T.; Moorman, N. J.; Madden, E. A.; Taft-Benz, S. A.; Anderson, E. J.; Sanders, W. A.; Dickmander, R. J.; Baxter, V. K.; Baylin, S.; Wurtele, E.; Moraes-vieira, P.; Taylor, D.; Mason, C.; Schisler, J. C.; Schwartz, R. E.; Beheshti, A.; Wallace,

doi:10.1101/2022.02.19.481089

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bioRxiv · 10.1101/2022.02.19.481089

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

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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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Guarnieri, J. W., Dybas, J. M., Fazelinia, H., Kim, M. S., Frere, J., Zhang, Y., Albrecht, Y. S., Murdock, D. G., Angelin, A., Singh, L. N., Weiss, S. L., Best, S. M., Lott, M. T., Cope, H., Zaksas, V., Saravia-Butler, A., Meydan, C., Foox, J., Mozsary, C., Kidane, Y. H., Priebe, W., Emmett, M., Meller, R., Singh, U., Bram, Y., tenOever, B. R., Heise, M. T., Moorman, N. J., Madden, E. A., Taft-Benz, S. A., Anderson, E. J., Sanders, W. A., Dickmander, R. J., Baxter, V. K., Baylin, S., Wurtele, E., Moraes-vieira, P., Taylor, D., Mason, C., Schisler, J. C., Schwartz, R. E., Beheshti, A., Wallace,. 2022-02-22. Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection. https://doi.org/10.1101/2022.02.19.481089

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