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

病毒感染可以诱导特异性转移RNA片段（trf）的形成，这些片段被包装并从宿主细胞外泌体中释放出来。该项目旨在发现外泌体tRFs的生物学作用，特别是研究这些tRFs进入未感染细胞是否会触发针对SARS-CoV-2和其他呼吸道RNA病毒的先天抗病毒免疫反应。对trf对宿主防御病毒感染机制影响的新见解可以用于对抗COVID-19和未来相关病毒的爆发。该项目还为研究生和本科生提供培训机会，后者通过生物信息学课程为基础的研究。该项目基于初步数据，表明tRF外泌体递送构成先天性抗病毒免疫的新机制，其中tRF为宿主细胞提供更强大的干扰素应答。对SARS-CoV-2的研究将以具体问题为指导，例如，受体细胞对外泌体tRF的摄取程度和生物利用度，tRF是否与病毒rna杂交并通过与rig - 1的关联激活干扰素的产生，以及细胞内tRF是否抑制病毒在细胞中的复制。新的宿主防御机制的表征可能为针对COVID-19的治疗干预策略提供信息。该RAPID奖由分子和细胞生物科学部遗传机制计划和刺激竞争研究的既定计划（EPSCoR）共同资助，资金来自《冠状病毒援助、救济和经济安全（CARES）法案》。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.