Project 458542

A novel coronavirus, named SARS-CoV-2, emerged in late 2019, and the resulting pandemic has caused global devastation. This virus causes COVID, which presents with a wide range of symptoms, as some individuals are completely asymptomatic or have only mild illness while others develop severe disease leading to hospitalization or death. Advanced age is the greatest risk factor for severe illness; however, aside from that, we do not understand precisely why the disease manifests so severely in some and not in others. New data suggest that an inappropriate immune response to SARS-CoV-2 is responsible for severe disease. When cells are first infected with a virus, they activate anti-viral genes to decrease viral replication in the infected cell and prevent infection of neighbouring cells. Emerging evidence suggests that during SARS-CoV-2 infection, the anti-viral responses that should normally occur early in infection are weak and delayed. When this anti-viral response is diminished, the inflammatory immune response that follows is overreactive and can cause severe tissue damage and disease. With this scholarship, I propose to study the role of cellular granules called processing bodies, which until now were not appreciated to be connected to our antiviral response. We showed that SARS-CoV-2 and other human coronaviruses cause processing bodies to disappear during infection, suggesting that there is an important reason that these viruses want processing bodies to be gone. Processing bodies control cellular immune protein production, and in this way, their disappearance may contribute to the imbalanced immune responses associated with severe COVID. With this proposal, I want to elucidate how processing body disruption is advantageous for the virus and to determine if we can reduce SARS-CoV-2 growth or infection by enhancing antiviral processing body formation.