RAPID: Exosomal tRNA fragments may constitute an innate viral defense against SARS-CoV-2 and other respiratory RNA viruses.

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Viral infection can induce formation of specific transfer RNA fragments (tRFs) that are packaged and released from host cells in exosomes. The project aims to discover the biological role of exosomal tRFs, specifically investigating whether uptake of these tRFs into uninfected cells triggers an innate antiviral immune response against SARS-CoV-2 and other respiratory RNA viruses. New insights into the influence of tRFs on host defense mechanisms against viral infections could be exploited to combat COVID-19 and future outbreaks of related viruses. The project also offers training opportunities for graduate and undergraduate students, the latter through bioinformatics course-based research.The project is based on preliminary data suggesting that tRF exosomal delivery constitutes a novel mechanism of innate antiviral immunity whereby tRFs prime host cells for a more robust interferon response. The research on SARS-CoV-2 will be guided by specific questions, for example, about the extent of exosomal tRF uptake and bioavailability in recipient cells, whether the tRFs hybridize with viral RNAs and activate interferon production through association with RIG-I, and whether intracellular tRFs inhibit viral replication in cells. Characterization of a novel host defense mechanism could potentially inform strategies for therapeutic intervention against COVID-19. This RAPID award is jointly funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competitive Research (EPSCoR), using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.