Tuesday, October 21, 2025 10/21/2025

TRAF3 regulation in antiviral host defense

Award Number: R21AI178469
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: 05/22/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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TRAF3 regulation in antiviral host defense - Project Summary The induction of type I interferon (IFN-I) cytokines plays an essential role in the innate immune response to virus infections by eliciting an antiviral gene program that facilitates the suppression of virus replication and spread. Cytosolic detection of viral nucleic acids by germ-line encoded pattern recognition receptors (PRRs) serves as an initial first step in activating the IFN-I response. Emerging studies however, have linked previously unknown roles for DNA sensing PRRs in detecting aberrant DNA species of self-origin to trigger the onset of age-related diseases, neurological disorders, and autoinflammatory conditions in the absence of infection. Thus, there is a critical need to delineate the mechanisms by which nucleic acid sensing PRRs control IFN-I activation to develop the next generation of therapeutics to combat viral infections as well as DNA damage driven disease states. We have recently identified a novel cross-talk phenomenon between cytosolic nucleic acid sensing PRRs that activate IFN-I and the non-canonical NF-κB pathway. While the non-canonical NF-κB pathway primarily governs lymphoid organogenesis and B-cell survival and maintenance in response to extracellular ligation of select members of the TNF receptor superfamily, our data unexpectedly revealed that intracellular ligation of nucleic acid sensing cytosolic PRRs also resulted in non-canonical NF-κB activation by causing the turnover of TNF receptor associated factor 3 (TRAF3), a key component of a steady-state negative regulatory complex that persistently causes the destabilization of the non-canonical NF-ĸB inducing kinase (NIK) which initiates signaling to the non-canonical NF-ĸB transcription factor complex. Our preliminary data further established that TRAF3 and NIK operate as differential regulators of IFN-I activation downstream of RNA and DNA sensing cytosolic PRRs. However, the mechanisms by which TRAF3 and NIK are controlled to modulate non-canonical NF-κB and IFN-I activation upon nucleic acid detection by cytosolic PRRs are poorly defined. Here we interrogated published data sets that examined TRAF3 and NIK protein interaction networks with a goal of identifying novel candidates with the potential to modulate how the non-canonical NF-κB pathway undergoes activation during cytosolic nucleic acid signaling and how the non-canonical NF-κB effector, NIK cross-talks with the IFN-I signaling platform. We identify synaptosome associated protein 29 (SNAP29) as a TRAF3 interacting partner and seek to characterize how SNAP29 modulates TRAF3 function in the context non-canonical NF-ĸB and IFN-I pathway activation. Our studies will help define new regulatory elements that control not only antiviral host defense programs, but also immune development and age related autoinflammatory disease states triggered by DNA damage or chromosomal instability.


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: 2025 ( Subtotal = $0 )
2025	2024	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	2	8/26/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $191,250 )
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	2	4/22/2024	NON-COMPETING CONTINUATION	$191,250
														Subtotal = $191,250

Issue Date FY: 2023 ( Subtotal = $229,250 )
2023	2023	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	1	5/22/2023	NEW	$229,250
														Subtotal = $229,250

Grand Total All Awards = $420,500

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TRAF3 regulation in antiviral host defense

Award Number: R21AI178469

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: 05/22/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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