SARS-CoV2 Proteins Alter the Mitochondria-Associated Membrane, a Structure that Controls Neuroinflammation

The 2019 coronavirus disease (COVID-19) is an infectious disease, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infects cells of the airways. Additionally, coronaviruses are known to activate inflammatory signaling pathways and cause dysfunction of the brain (neuroinflammation). To address brain defects within COVID-19 patients, a better understanding of the consequences of SARS-CoV2 would be beneficial. The Simmen Lab has previously identified an intracellular structure known as the mitochondria-associated membrane (MAM) as a key control station of neuroinflammation. This structure controls the energy output of mitochondria, but also promotes inflammation. We hypothesized that COVID-19 could trigger the same effect, because several SARS-CoV2 proteins, including ORF8, are known to colocalize with MAM proteins. Indeed, preliminary results from the lab have indicated that SARS-CoV2-infected human cells show changes to the mitochondrial structures and have hallmarks of cell stress. I therefore hypothesize that a subset of SARS-CoV2 proteins compromise the control of mitochondria through the disruption of MAM proteins. To test this hypothesis, I will express SARS-CoV2 proteins in different human cells systems and observe the structure of MAM. Next, I will monitor cellular energy, stress levels, and inflammatory levels. Using different brain cell types, I will test whether response also occurs in these cells and whether it can be transmitted from one cell type to another, a frequent event during neuroinflammation.