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Identification of SIV replication and reservoirs in the CNS

Award Number: R01MH125395
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Identification of SIV replication and reservoirs in the CNS - Abstract Even though highly potent antiretroviral therapy (ART) has the ability to reduce viral replication to undetectable levels in the plasma in simian immunodeficiency virus (SIV) infected monkeys, our recently developed viral env directed immunoPET/CT imaging technology has been able to detect foyers of continued SIV signals even after prolonged ART. However, the ability of this non-invasive technique to map SIV signal in the CNS have thus far been elusive. In this application we propose to focus on the development of probes and strategies to specifically address SIV signals in the CNS, by optimizing the technology to enable SIV specific PET probes to cross the blood brain barrier and mark cells expressing SIV env in vivo. Towards this goal we will use the pigtailed macaque model infected with SIVsmB670/SIVmac239-17E-Fred developed and validated by the team of Dr. Clements as one of the most reliable models of neuroHIV. Leveraging the strength and technological advances available at the New Iberia Research Center and Georgia Tech, we will map the seeding of reservoirs in the CNS during acute infection and monitor the kinetic of viral signals post-acute infection using a combination of immunoPET/CT, light-sheet and confocal imaging techniques, as well as sorting of infected cells to document the nature and function of cells remaining active in the early chronic phase of CNS SIV infection. Next we will document the dynamics of viral kinetics in the CNS relative to total body upon ART initiation, as well as post- ART interruption. Data generated from these highly detailed analyses will delineate which cells retain persistent viral replication under ART (if any) and more importantly evaluate the contribution of CNS viral reservoirs to the early viral rebound in vivo. The in depth analysis of this data will also provide important steps towards the development of cure strategies that include the CNS.


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: 2024 ( Subtotal = $784,326 )
2024	2024	UNIVERSITY OF LOUISIANA AT LAFAYETTE	104 E UNIVERSITY AVE	LAFAYETTE	LA	70503	LAFAYETTE	USA	Mental Health Research Grants	000	5	8/1/2024	NON-COMPETING CONTINUATION	$784,326
														Subtotal = $784,326

Issue Date FY: 2023 ( Subtotal = $785,354 )
2023	2023	UNIVERSITY OF LOUISIANA AT LAFAYETTE	104 E UNIVERSITY CIR 3RD FL	LAFAYETTE	LA	70503	LAFAYETTE	USA	Mental Health Research Grants	000	4	8/11/2023	NON-COMPETING CONTINUATION	$785,354
														Subtotal = $785,354

Issue Date FY: 2022 ( Subtotal = $838,128 )
2022	2022	UNIVERSITY OF LOUISIANA AT LAFAYETTE	104 E UNIVERSITY CIR 3RD FL	LAFAYETTE	LA	70503	LAFAYETTE	USA	Mental Health Research Grants	000	3	7/20/2022	NON-COMPETING CONTINUATION	$838,128
														Subtotal = $838,128

Issue Date FY: 2021 ( Subtotal = $838,128 )
2021	2021	UNIVERSITY OF LOUISIANA AT LAFAYETTE	104 E UNIVERSITY CIR 3RD FL	LAFAYETTE	LA	70503	LAFAYETTE	USA	Mental Health Research Grants	000	2	7/16/2021	NON-COMPETING CONTINUATION	$838,128
														Subtotal = $838,128

Issue Date FY: 2020 ( Subtotal = $875,438 )
2020	2020	UNIVERSITY OF LOUISIANA AT LAFAYETTE	104 E UNIVERSITY CIR 3RD FL	LAFAYETTE	LA	70503	LAFAYETTE	USA	Mental Health Research Grants	000	1	9/19/2020	NEW	$875,438
														Subtotal = $875,438

Grand Total All Awards = $4,121,374

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Identification of SIV replication and reservoirs in the CNS

Award Number: R01MH125395

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/19/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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