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Prenylation in antiviral immunity

Award Number: R01AI175724
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/14/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Prenylation in antiviral immunity - Summary In this proposal, we will explore the role of prenylation in antiviral immunity. Prenylation is a post-translational modification that renders proteins hydrophobic, thus targeting them to the endomembrane. While the role of prenylation in immunity is unclear, our preliminary data shows compelling evidence that prenylation is a modification widely used in innate antiviral immunity. As both the host and virus utilize prenylation and the cholesterol biosynthetic pathway, we propose a dynamic host-pathogen interaction at this interface. We hypothesize that prenylation could be a potent host innovation to counter viral pathogenesis. This is based on in silica analysis that revealed an enrichment of immunity-related proteins with a prenylation motif. We followed in-silica analyses with a biochemical screen and identified several prenylated antiviral proteins that are involved in interferon responses and virus restriction, with potential to affect virus entry, replication, and egress. In this grant, we propose to identify the functional consequences of prenylated proteins on subcellular localization, interferon signaling, and antiviral function. By perturbing specific enzymes in the prenylation pathway, we will study its effect on interferon response, antiviral effectors, and virus control. This work will provide novel insights into cell-intrinsic antiviral countermeasures and the development of novel antiviral drug targets.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $627,662 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	4	12/30/2025	NON-COMPETING CONTINUATION	$627,662
														Subtotal = $627,662

Issue Date FY: 2025 ( Subtotal = $611,151 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	3	2/12/2025	NON-COMPETING CONTINUATION	$611,151
														Subtotal = $611,151

Issue Date FY: 2024 ( Subtotal = $632,371 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	001	2	5/24/2024	NON-COMPETING CONTINUATION	$63,237
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	2	12/20/2023	NON-COMPETING CONTINUATION	$569,134
														Subtotal = $632,371

Issue Date FY: 2023 ( Subtotal = $646,625 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	1	2/14/2023	NEW	$646,625
														Subtotal = $646,625

Grand Total All Awards = $2,517,809

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Prenylation in antiviral immunity

Award Number: R01AI175724

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/14/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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