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CD4 T cell control of cytomegalovirus

Award Number: R01AI139749
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: 02/07/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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CD4 T cell control of cytomegalovirus - Summary Cytomegalovirus (CMV, a b-herpesvirus) establishes a persistent infection that is endemic in humans and mice. CMV causes acute clinical disease only if immunity is naïve or compromised, exemplifying how coevolution with its host over millennia has resulted in a largely non-pathogenic détente. However, this `percolating' infection imposes a huge footprint on the immune system, especially the T cell memory pool, and growing evidence suggests this may ultimately be detrimental. Mounting a rapid CD4 T cell response correlates with protection from CMV-associated disease and reduced viral shedding. Our lab identified the first mouse CMV (MCMV) epitope-specific CD4 T cells. Of these, one response against the viral M09 protein expands long after systemic viral infection is controlled, and is critical for resolving the persistent-phase of CMV replication. Our new data show these `late-rising' M09 cells are unique with regards to their phenotype, effector function and transcriptome when compared to conventional CD4 T cells that expand early during infection. Additionally, vaccine-induced late-rising CD4 T cells provide potent protection against CMV challenge. Our overarching hypothesis is that distinct immune environments during the acute and persistent phases of CMV infection promote the expansion/differentiation of these late-rising cells that ultimately resolve persistence and promote latency establishment. We will determine why these cells show such delayed expansion, determine whether they use unique mechanisms of cytolysis to kill infected cells and resolve persistence and initiate studies to determine whether similar CD4 T cells exist in CMV infected people. Together this proposal represents a comprehensive plan using unique viral tools and omics-based approaches to elucidate how newly identified late-rising CD4 T cells function to resolve persistent CMV replication, a question that has remained largely unaddressed to date.


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	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	5/22/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $565,653 )
2023	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	12/21/2022	NON-COMPETING CONTINUATION	$565,653
														Subtotal = $565,653

Issue Date FY: 2022 ( Subtotal = $615,063 )
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	1/13/2022	NON-COMPETING CONTINUATION	$615,063
														Subtotal = $615,063

Issue Date FY: 2021 ( Subtotal = $615,063 )
2021	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	1/15/2021	NON-COMPETING CONTINUATION	$615,063
														Subtotal = $615,063

Issue Date FY: 2020 ( Subtotal = $720,659 )
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	1/29/2020	NON-COMPETING CONTINUATION	$720,659
														Subtotal = $720,659

Issue Date FY: 2019 ( Subtotal = $720,659 )
2019	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	2/6/2019	NEW	$720,659
														Subtotal = $720,659

Grand Total All Awards = $3,237,097

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CD4 T cell control of cytomegalovirus

Award Number: R01AI139749

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: 02/07/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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