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Uncovering and harnessing connected metabolic pathways essential to virus infection.

Award Number: R35GM138199
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Uncovering and harnessing connected metabolic pathways essential to virus infection. - Project Summary / Abstract Polyamines are small molecules abundant in eukaryotic cells that function in transcription and translation. While these molecules are important for cellular function, emerging evidence suggests that polyamine metabolism is intricately linked to diverse metabolic pathways within the cell. The interconnectedness of metabolic pathways has significant consequences for cells, as well as pathogens. We previously demonstrated that polyamines support replication of diverse RNA viruses and that upon detection of infection, cells induce polyamine depletion. Polyamine depletion limits infection by bunyaviruses (Rift Valley fever virus [RVFV] and La Crosse virus [LACV]), flaviviruses (Zika virus [ZIKV] and dengue viruses), and enteroviruses (Coxsackievirus B3 [CVB3], rhinovirus), among several others. We hypothesize that these distinct virus families subvert cellular metabolism, specifically through polyamines, to support virus replication. Here, we will investigate (1) how viruses utilize polyamines at distinct stages of replication, (2) how viruses confront polyamine depletion, and (3) how polyamine biosynthesis connects to other metabolic pathways to support virus replication. We use the RVFV, ZIKV, and CVB3 model systems in our work because these viruses represent three evolutionarily distant viruses with different replicative and structural differences. While each of these viruses relies on polyamines for replication, we find that how they use polyamines is different. Now, we will expand on this work to understand the roles of distinct polyamines during virus infection, including roles in virion structure, cellular attachment, and genome replication. We will also use these model systems to understand how these viruses manipulate polyamine metabolism. Finally, we will investigate how the differences in polyamine utilization may reflect how polyamines affect other cellular metabolic pathways, including lipid and cholesterol synthesis. This work will illuminate the connectedness of polyamine biosynthesis to other metabolic pathways and how viruses rely on these interconnected pathways for successful replication. This work will highlight fundamental roles for polyamines in virus replication and in cellular metabolism.


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 = $0 )
2026	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	5	3/30/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $414,577 )
2025	2025	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	6	8/13/2025	COMPETING CONTINUATION	$414,577
														Subtotal = $414,577

Issue Date FY: 2024 ( Subtotal = $369,351 )
2024	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	5	8/26/2024	NON-COMPETING CONTINUATION	$369,351
														Subtotal = $369,351

Issue Date FY: 2023 ( Subtotal = $369,351 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	4	9/12/2023	NON-COMPETING CONTINUATION	$369,351
														Subtotal = $369,351

Issue Date FY: 2022 ( Subtotal = $369,351 )
2022	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	3	8/12/2022	NON-COMPETING CONTINUATION	$369,351
														Subtotal = $369,351

Issue Date FY: 2021 ( Subtotal = $369,351 )
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	2	8/26/2021	NON-COMPETING CONTINUATION	$369,351
														Subtotal = $369,351

Issue Date FY: 2020 ( Subtotal = $368,430 )
2020	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	1	7/30/2020	NEW	$368,430
														Subtotal = $368,430

Grand Total All Awards = $2,260,411

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Uncovering and harnessing connected metabolic pathways essential to virus infection.

Award Number: R35GM138199

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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