Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The impact of HIV LTR intra- and inter-individual sequence variability on HIV latency and reactivation dynamics

Award Number: R56AI203669
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

The impact of HIV LTR intra- and inter-individual sequence variability on HIV latency and reactivation dynamics - Summary Persistent latent HIV-1 reservoirs pose a major challenge to the eradication of HIV as they enable rapid viral rebound upon interruption of antiretroviral therapies. Multiple mechanisms contribute to limited proviral expression, HIV-1 latency, and HIV-1 proviral transcriptional reactivation, including recruitment of cellular transcription factors, epigenetic regulation, and RNA polymerase II pause release. Current shock and kill strategies, aimed at reactivating and then eliminating these reservoirs, have been only partially successful due to their failure to effectively target the broad genetic and transcriptional proviral variability within latent reservoirs. To address these challenges, we propose a strategy for exploring the mechanisms of HIV-1 latency establishment and reactivation across assorted HIV isolates from multiple clades, with the ultimate goal of improving the effectiveness of therapeutic interventions targeting the persistent reservoir. Our preliminary studies show extensive transcriptional activity variability of long-terminal repeats (LTRs) across ~6,000 HIV-1 isolates and clades using massively parallel reporter assays (MPRAs). These initial studies have identified LTRs from clades with higher activity, LTR regions responsible for the variable activity, and transcription factors contributing to LTR function. The proposed research builds upon this work and is structured around three specific aims. The first aim will determine how LTR activity across HIV-1 isolates impacts provirus expression and the establishment of HIV-1 latency. We will generate a library of viruses that have 158 representative LTRs reflecting the different transcription factor configurations and clades identified by MPRAs to examine how LTRs and local chromatin environment influence proviral transcription and the establishment of latency. The second aim will focus on mechanisms that reactivate LTRs that represent different clades in response to different latency reversal agents, testing the hypothesis that differential responses to latency reversal agents reflect LTR and the chromatin environment of integration sites. The goal of the third aim is to develop predictive models of LTR activity and utilize clinical samples from people with HIV to test these models. Aim 3 will provide insights into how sequence features and kinetic parameters evolve during infection and treatment. Successful completion of this proposed work will provide a better understanding of how HIV transcription is regulated across a diverse array of HIV-1 clinical isolates and clades, as well as provide new approaches to evaluate compounds designed to target the HIV reservoir.


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 = $765,050 )
2026	2026	BOSTON MEDICAL CENTER CORPORATION	1 BOSTON MEDICAL CTR PL	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	8/20/2026	NEW	$765,050
														Subtotal = $765,050

Grand Total All Awards = $765,050

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The impact of HIV LTR intra- and inter-individual sequence variability on HIV latency and reactivation dynamics

Award Number: R56AI203669

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer