Elucidating the interplay between mitochondrial dynamics, membrane contact sites and SARS-CoV-2 viral infection driving inflammation

The last decade has witnessed repeated emergence of RNA viruses with high pathogenic potential in humans including SARS-CoV-2, Zika virus, yellow fever virus and Ebola virus. The inflammatory response to infection is a major driver of pathogenesis, but the molecular mechanisms by which these viruses initiate and dysregulate inflammation are not well defined. Mitochondria have emerged as critical regulators of the immune system and inflammation, serving as both signaling platforms and as sources of danger-associated molecular patterns (DAMPs) to initiate diverse signaling pathways. SARS-CoV-2, like other positive stranded RNA viruses, uses membranes derived from the ER for their replication factories, but also actively manipulates mitochondria, Golgi apparatus and other membrane bound organelles for replication purposes. However, it is unclear why mitochondria are hijacked during viral replication, and what are the consequences of this manipulation to inter-organelle communication and inflammation. In this project, in collaboration with Pr. Sonja Best (NIAID/NIH), we will use different SARS-CoV-2 infection models coupled to cutting-edge microscopy analysis to determine novel ways in which mitochondrial membrane remodelling and organelle contact sites are controlled and the importance of these events as drivers of inflammation.