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Role of myeloid cells in CNS and systemic reservoirs and rebound

Award Number: R01MH125778
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Role of myeloid cells in CNS and systemic reservoirs and rebound - Project Summary/Abstract Despite the remarkable success of the combined antiretroviral therapy (cART) to control HIV-1 infection, viral reservoirs persist indefinitely under treatment. These persisting viral populations constitute the principal burden for an effective HIV-1 cure, as they lead to a rapid rebound in viremia when treatment fails or after analytic treatment interruption (ATI). Although persisting viral populations in tissue comprise most of the reservoir, the majority of the reservoir studies do not include tissue samples due to the difficulties to obtain tissue samples containing active foci of replication, the site of the rebounding virus. Therefore, we are not able to properly study these viral populations and their main characteristics remain unknown. Understanding the nature and properties of rebound should bring us a step closer to identifying the reservoir associated with persistence and rapid rebound after ATI. Our previous studies defining the early foci of rebound after ATI revealed an unexpected result as all detected SIV infected cells has a myeloid morphology and stained negative for CD3 and other T cell markers. Those studies were focused on the early reservoir, established when cART is initiated 4 days post challenge. Under these conditions, there are no virus specific cell mediated or humoral immune responses. However, at his point is clear that rebounding virus populations are filtered by immune responses in play when cART was initiated. Based on critical consideration and better model infection in humans, this project will determine the impact of innate and adaptive immune pressure impacts the milieu of the emerging foci in tissues leveraging our PET/CT guided necropsy and resection surgery workflow allowing the study of viral rebound within tissue during the eclipse phase. We intend to use our ability to localize SIV active viremia sites in infected macaques, to perform a detailed identification of the cells and anatomical compartments that support rebound of persistent SIV. We will study the effect of the innate and adaptive immune system and disrupt myeloid cell populations to determine the impact on the kinetics, magnitude, and viral population dynamics during rebound. The proposed project is scientifically relevant in its innovative approach and methodologies as it will allow to determine the main properties and dynamics the eclipse phase of rebound of persistent viral population after ATI. Given the importance of persistent viral populations in rebound. A better understanding of rebound virus population dynamics after ATI is key to developing successful strategies to cure HIV-1.


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 = $896,082 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	4	11/29/2024	NON-COMPETING CONTINUATION	$896,082
														Subtotal = $896,082

Issue Date FY: 2024 ( Subtotal = $1,026,035 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	3	11/22/2023	NON-COMPETING CONTINUATION	$923,431
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	001	3	8/30/2024	NON-COMPETING CONTINUATION	$102,604
														Subtotal = $1,026,035

Issue Date FY: 2023 ( Subtotal = $1,055,701 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	2	1/25/2023	NON-COMPETING CONTINUATION	$1,055,701
														Subtotal = $1,055,701

Issue Date FY: 2022 ( Subtotal = $1,064,451 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	001	1	2/8/2022	NEW	$0
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	1	12/14/2021	NEW	$1,064,451
														Subtotal = $1,064,451

Grand Total All Awards = $4,042,269

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Role of myeloid cells in CNS and systemic reservoirs and rebound

Award Number: R01MH125778

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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