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Defining Mechanisms for Parasite-Driven Effects on Gamma-Herpesvirus Latency

Award Number: R01AI130020
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: 08/10/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Defining Mechanisms for Parasite-Driven Effects on Gamma-Herpesvirus Latency - PROJECT SUMMARY The goal of this grant is to understand how bystander infections with intestinal parasites alter chronic infection with γ-herpesviruses. This is important because herpesviruses infect virtually all people and approximately a quarter of the world’s population is simultaneously infected with a parasite. Herpesvirus infections are chronic, but these viruses do not persistently replicate in a healthy host. Instead, they establish a quiescent infection, termed latency. We discovered previously that co-infection with an intestinal helminth parasite after infection with γ-herpesvirus led to increased virus reactivation from latency. We detailed a mechanism whereby reactivation of the virus depended on sensing host cytokines produced in response to the parasite. A remaining question is whether the timing of the dual infections is important. In this grant we propose to address this question by changing the order of virus-parasite co- infection to determine whether reactivation of the virus is increased by parasite infection when the parasite infection occurs before the γ-herpesvirus infection. We have data to indicate that prior infection with an intestinal parasite increases γ-herpesvirus reactivation, but that the mechanism is different than what we discovered previously when parasite infection occurs after the herpesvirus infection. We find that parasite infected animals have increased resident peritoneal macrophages. We also find that when retinoic acid, which is required for maintenance of resident peritoneal macrophages, is depleted in mice, parasite infection no longer increases virus reactivation. Our hypothesis is that parasite infection, in a retinoic acid dependent manner, alters the tissue composition of resident macrophages. This promotes retention of a population of infected macrophages with enhanced γ-herpesvirus reactivation. In this proposal, we aim to examine the role of resident macrophages and retinoic acid in parasite-induced herpesvirus reactivation. These studies will deliver insight into the mechanisms that drive herpesvirus reactivation during co-infection and will increase our understanding of parasite modulation of tissue resident macrophages. Harnessing the power of mouse model pathogens, these studies will advance our understanding of pathogen co-infection.


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 = $470,420 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	7	1/17/2025	NON-COMPETING CONTINUATION	$470,420
2025	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	001	6	4/21/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $470,420

Issue Date FY: 2024 ( Subtotal = $562,975 )
2024	2024	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	6	12/22/2023	NON-COMPETING CONTINUATION	$436,473
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	004	6	5/23/2024	NON-COMPETING CONTINUATION	$48,495
2024	2024	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	001	6	3/20/2024	SUPPLEMENT FOR EXPANSION	$78,007
2024	2023	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	003	5	3/28/2024	COMPETING CONTINUATION	$256,641
2024	2021	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	002	4	3/28/2024	NON-COMPETING CONTINUATION	-$256,641
														Subtotal = $562,975

Issue Date FY: 2023 ( Subtotal = $484,968 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	001	5	2/21/2023	COMPETING CONTINUATION	$484,968
2023	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	4	2/10/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $484,968

Issue Date FY: 2021 ( Subtotal = $405,000 )
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	4	7/8/2021	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2020 ( Subtotal = $486,729 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	3	6/22/2020	NON-COMPETING CONTINUATION	$405,000
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	001	3	8/19/2020	SUPPLEMENT FOR EXPANSION	$81,729
														Subtotal = $486,729

Issue Date FY: 2019 ( Subtotal = $405,000 )
2019	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	2	7/16/2019	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2018 ( Subtotal = $405,000 )
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	1	8/3/2018	NEW	$405,000
														Subtotal = $405,000

Grand Total All Awards = $3,220,092

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Defining Mechanisms for Parasite-Driven Effects on Gamma-Herpesvirus Latency

Award Number: R01AI130020

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: 08/10/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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