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

Effects of Cell-Intrinsic Immunity on Establishment and Reversal of HIV Latency

Award Number: R01AI150449
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: 09/01/2015
PERIOD OF PERFORMANCE END DATE: 08/31/2021

Group Awards By:

View Award Description

Effects of Cell-Intrinsic Immunity on Establishment and Reversal of HIV Latency - DESCRIPTION (provided by applicant): While the advent of antiretroviral therapy (ART) has dramatically reduced the morbidity and mortality associated with HIV infection, viral eradication is not achievable due to the persistence of latently-infected cells during treatment. ART must therefore be taken on a lifelong basis. Accumulating data suggest that HIV- infected individuals often experience persistent immune dysregulation, chronic inflammation, and accelerated aging even in the setting of ART-mediated viral suppression. These realities have created a pronounced interest in developing strategies to eradicate HIV in infected individuals. Identifying host determinants governing viral latency and reservoir size in vivo will be critical in developing effective strategies to clear the latent reservoir and cure HIV infection. Several cell-intrinsic immune factors have been discovered that restrict HIV infection in the absence of antiretroviral drugs. We recently demonstrated that the elevated expression of two particular restriction factors, p21 (inhibitor of HIV transcription) and schlafen 11 (codon usage-based inhibitor of HIV protein synthesis), was strongly associated with decreased HIV latent reservoir size in ART-suppressed individuals. We further demonstrated that select cell-intrinsic immune responses were enhanced in subjects who initiated ART during early versus chronic infection, likely contributing to the reduced reservoir size observed in these individuals. In this R01 project, we will extend our in vivo observations by performing single cell-level analyses, as well as ex vivo and in vitro experiments to characterize the effects of select host restriction factors on the establishment and reversal of HIV latency. In Aim 1, we will apply novel PCR-Activated Cell Sorting (PACS) technology to clinical samples from HIV-infected, ART-suppressed individuals to interrogate single CD4+ T cells for the presence of HIV DNA and RNA. We will then measure the expression of p21 and schlafen 11 in single cells harboring transcriptionally active and inactive proviruses to elucidate the role of these factors in regulating viral latency. In Aim 2, w will use lentiviral transduction to overexpress and silence select cell- intrinsic immune factors i primary cells and human lymphoid aggregate cultures (HLAC). A dual-reporter HIV construct will then be used to examine the effects of these cell-intrinsic immune factors on the establishment of latent HIV infection. Lastly, in Aim 3, we will manipulate p21 and schlafen 11 expression in a cell line model of HIV latency and in HIV-infected primary cells. Cells will then be treated with a comprehensive panel of latency reversal agents, to examine the effects of p21 and schlafen 11 manipulation on the efficacy of these agents and on the dynamics of viral reactivation. This study will yield valuable insights into how cell-intrinsic immunity may serve as a foundation of novel curative strategies for HIV infection.


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: 2023 ( Subtotal = $0 )
2023	2019	VITALANT	9305 E VIA DE VENTURA	SCOTTSDALE	AZ	85258	MARICOPA	USA	Biomedical Research and Research Training	000	5	11/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = -$301 )
2022	2019	VITALANT	6210 E OAK ST	SCOTTSDALE	AZ	85257	MARICOPA	USA	Biomedical Research and Research Training	000	5	4/4/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$301
														Subtotal = -$301

Issue Date FY: 2019 ( Subtotal = $304,810 )
2019	2019	VITALANT	6210 E OAK ST	SCOTTSDALE	AZ	85257	MARICOPA	USA	Biomedical Research and Research Training	000	5	8/1/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$304,810
														Subtotal = $304,810

Grand Total All Awards = $304,509

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Effects of Cell-Intrinsic Immunity on Establishment and Reversal of HIV Latency

Award Number: R01AI150449

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: 09/01/2015

PERIOD OF PERFORMANCE END DATE: 08/31/2021

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer