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

Viral Genetic Determinants of HIV Transcription Control in the Context of HIV Cure

Award Number: R01AI203543
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: 08/30/2030

Group Awards By:

View Award Description

Viral Genetic Determinants of HIV Transcription Control in the Context of HIV Cure - PROJECT SUMMARY HIV persists during suppressive antiretroviral therapy (ART), and no curative intervention is currently available. All immune-based HIV cure strategies under active investigation, including latency reversal and antibody- mediated interventions, depend on viral gene expression to render infected cells detectable and eliminable. However, HIV transcription during ART is variable, and the viral determinants that govern transcriptional level, transcript composition, and responsiveness to latency-reversing agents remain incompletely defined. HIV transcription is regulated by viral elements encoded within the provirus, including the long terminal repeat (LTR) promoter, the Tat protein, and the TAR RNA element, which regulate transcriptional initiation and elongation. These viral regulatory elements are naturally polymorphic in circulating HIV-1. Prior studies have shown that variation in individual elements, such as promoter NFκB motif number or Tat sequence, can influence transcriptional activity in experimental systems, but these studies typically examine one element at a time, rely on molecular cloning or reporter assays in transformed cell lines, and do not account for viral integration site or host genetic background. Moreover, promoter, Tat, and TAR variation have not been evaluated together in direct ex vivo clinical samples. The goal of this project is to determine how naturally occurring viral polymorphisms in regulatory elements including the promoter, Tat, and TAR contribute to HIV transcriptional output and latency reversal responsiveness under ART. Using ex vivo CD4⁺ T cells from individuals on suppressive ART, we will quantify viral regulatory genotypes and measure HIV transcriptional levels, transcript class distributions, and responses to mechanistically distinct latency-reversing agents (Aim 1). To establish whether observed transcriptional phenotypes are intrinsic to viral genotype or confounded by proviral integration site and chromosomal context, we will complement clinical analyses in Aim 1 with a controlled experimental system in which viruses with defined regulatory genotypes are evaluated across diverse integration sites in primary CD4⁺ T cells (Aim 2). Together, these studies will define the contribution of viral polymorphisms to HIV transcriptional heterogeneity during ART and establish whether viral genotype represents a biologically meaningful variable for HIV cure strategy design.


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 = $3,375,319 )
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	8/25/2026	NEW	$3,375,319
														Subtotal = $3,375,319

Grand Total All Awards = $3,375,319

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Viral Genetic Determinants of HIV Transcription Control in the Context of HIV Cure

Award Number: R01AI203543

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: 08/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer