Award Abstract #2030080

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

NSF Directorate:
BIO - Directorate for Biological Sciences
NSF Division:

Division of Molecular and Cellular Biosciences

Initial Amendment Date:

Latest Amendment Date:

Award Number:

2030080

Award Instrument:

Grant

Program Manager:

Arcady Mushegian

Start Date:

End Date:

Awarded Amount to Date:

$231,020.00

Investigator(s):

Glen M Borchert [email protected] (Principal Investigator)
Jin H Kim (Co-Principal Investigator)

Sponsor:

University of South Alabama
307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG
MOBILE AL 366883053

NSF Program:
Genetic Mechanisms
EPSCoR - Established Program to Stimulate Competitive Research Funding
COVID-19 Research
Program Reference Code(s):
096Z
7465
7914
9150
Program Element Code(s):
158Y
9150
Abstract:

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.