VCOM Research Day Program Book 2023

Graduate Student Research Biomedical

12 Calming the Storm: Anti-Inflammatory Protein NLRX1 and its Role in the Immune Response to SARS-CoV-2

Hannah Ivester 1 ; Holly Morrison 2 ; Juselyn Tupik 2 ; Christina Chuong 2 ; Carla Finkielstein 3 ; Nisha Duggal 2 ; James Weger 2 ; Irving Coy Allen 2 Corresponding author: Hivester@vt.edu

1Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg 2 Department of Biomedical Science and Pathobiology, Virginia Tech, Blacksburg 3 Fralin Biomedical Research Institute at VTC, Roanoke

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has certainly impacted the world in major ways since its emergence in December 2019. One of the most well-known clinical disease presentations of COVID-19 includes what has been called the ‘cytokine storm’ of severe disease. This dysregulated level of inflammation is also responsible for the Multisystem Inflammatory Syndrome that is seen in pediatric patients. One of the most important functions of the immune system is to be able to dampen the response to mitigate host tissue damage as a result of an overzealous immune activation. In cases of COVID-19 presenting with a ‘cytokine

storm,’ this ability to balance the immune response is lost, resulting in large amounts of tissue damage and more severe disease outcomes. One such protein responsible for negative regulation of the immune response is NLRX1, which has many roles within multiple arms of antiviral immunity. Here we show that deficiencies in NLRX1 result in differential immune responses to SARS-CoV-2 both in cell culture and in mice. These data report differences in viral clearance, clinical disease presentation, and immune activation- including cytokine production. In addition, further data might suggest that this protein could offer itself or other up- or downstream proteins

or complexes as a therapeutic targets to help mitigate the effects of the ‘cytokine storm’ related to severe COVID-19 disease. Finally, this data also adds to the growing body of evidence surrounding SARS-CoV-2 and its pathobiology in an understudied context of immune regulation and its importance in antiviral immunity.

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