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Viral In-depth Characterization Through Immunocapture to Identify the Cellular Sources and Genetic Diversity of the HIV-1 Reservoirs

Award Number: R21AI189222
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: 09/03/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Viral In-depth Characterization Through Immunocapture to Identify the Cellular Sources and Genetic Diversity of the HIV-1 Reservoirs - PROJECT SUMMARY Despite the remarkable success of antiretroviral therapy (ART) to control HIV-1 infection, viral reservoirs persist indefinitely under treatment. These remaining 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 is discontinued. Viral reservoirs in ART treated individuals are constituted by latently infected long-lived immune cells. Additionally, the reservoir comprises populations that produce low levels of viremia even in presence of high levels of ART. The sources of this residual viremia might play a key role in the fast “viral rebound” often observed after therapy cessation. Different studies demonstrate that the reservoirs are rapidly established early after infection and distributed throughout the body in multiple anatomical sites. In addition to T-CD4+ cells, a growing number of studies suggest that other T-cells and myeloid cells such as macrophages and mast cells constitute potential active and/or inducible reservoirs too. This capacity to establish reservoirs in a wide variety of cellular targets and anatomical compartments is promoted by HIV-1 accessory and regulatory proteins and might lead to viral characteristics directly associated with the producer cell type. In this proposal, we aim to characterize viruses produced by different cell types and their corresponding integrated provirus using tissue “ex vivo” infections. Furthermore, we will study the sources and characteristics of the viral particles that comprise the residual viremia from various anatomical compartments using clinical samples from people living with HIV-1 under ART. We will use our newly developed pipeline that combines viral immuno-capture (v-IC) from multiple cell types, with proviral sequencing in the same cell types, long-read deep viral sequencing, and viral particle multi-omics. This new pipeline will be very relevant for HIV-1 cure studies to identify the sources of viremia during ART and to better analyze the viral reservoirs.


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 = $200,000 )
2026	2026	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	2	8/20/2026	NON-COMPETING CONTINUATION	$200,000
														Subtotal = $200,000

Issue Date FY: 2025 ( Subtotal = $240,000 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	1	9/3/2025	NEW	$240,000
														Subtotal = $240,000

Grand Total All Awards = $440,000

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Viral In-depth Characterization Through Immunocapture to Identify the Cellular Sources and Genetic Diversity of the HIV-1 Reservoirs

Award Number: R21AI189222

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: 09/03/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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