Monday, June 30, 2025 6/30/2025

Single Cell Analysis of HIV-1 Latent reservoir establishment in Humanized Mice

Award Number: F30AI162222
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/24/2021
PERIOD OF PERFORMANCE END DATE: 11/23/2025

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Single Cell Analysis of HIV-1 Latent reservoir establishment in Humanized Mice - Abstract Human Immunodeficiency Virus (HIV) has infected 76 million people worldwide and caused the death of 38 million. Current treatments can reduce patient viral loads but fail to cure patients of infection. This is due to the ability of the virus to undergo latency during antiretroviral therapy. Latently infected cells are nearly indistinguishable from uninfected cells and there is no effective treatment to eliminate these cells. Our long- term goal is to describe at a single cell level, how early reservoir seeding occurs and the mechanisms that drive latency establishment. The proposed experiments in this grant are based on the hypothesis that during acute infection, a proportion of infected CD4+ T cells from diverse lineages of T cells such as resting CD4+ memory, activated T cells, naïve T cell, effector memory T cell undergo early latency and that transcriptional pathways such as mTOR and EIF2 signaling and provirus integration into transcriptionally repressive site are mechanisms of early latency establishment. This hypothesis is based on observations that: i) despite extremely early ART treatment, HIV latent reservoir may be established earlier than 72 hours after exposure ii) a diverse subset of T cells can harbor latent HIV iii) complex interactions between host and viral factors drive latency. First generation latency marking technology has been developed by the Chen lab to report the history of HIV infection through irreversible marking all HIV-infected cells called HIV-Induced Lineage Tracing (HILT). In this application, I propose a second-generation, innovative genetic marking technology, Enhanced HILT (EHILT), to further our knowledge the complexities of HIV latency. Using EHILT and validated small animal models of latency, I will define early latency kinetics in in vitro and in vivo acute and ART-treated infection using EHILT, identify transcriptional profiles and pathways associated with latency in vivo, and profile the integration sites of provirus with immediate latent phenotype.


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 = $53,974 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	4	11/8/2024	NON-COMPETING CONTINUATION	$53,974
														Subtotal = $53,974

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	002	3	5/6/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	3	11/6/2023	NON-COMPETING CONTINUATION	$52,694
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	001	3	11/20/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $46,094 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	11/9/2022	NON-COMPETING CONTINUATION	$45,152
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	001	2	2/24/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $46,094

Issue Date FY: 2022 ( Subtotal = $46,592 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	001	1	11/24/2021	NEW	$0
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	11/24/2021	NEW	$45,876
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	003	1	5/27/2022	NEW	-$1
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	002	1	5/10/2022	NEW	$717
														Subtotal = $46,592

Grand Total All Awards = $200,634

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Single Cell Analysis of HIV-1 Latent reservoir establishment in Humanized Mice

Award Number: F30AI162222

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/24/2021

PERIOD OF PERFORMANCE END DATE: 11/23/2025

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