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

How SAMHD1 regulates HIV-1 innate immunity and viral gene expression

Award Number: R01AI189220
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: 07/09/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2030

Group Awards By:

View Award Description

How SAMHD1 regulates HIV-1 innate immunity and viral gene expression - Abstract The lack of clear mechanisms by which host proteins regulate HIV-1 innate immunity in macrophages is a significant knowledge barrier to a functional cure for HIV-1 persistent infection. In this revised R01 proposal, we seek to investigate non-canonical functions of the cellular protein sterile alpha motif and HD domain-containing protein 1 (SAMHD1) in regulating innate immune responses during HIV-1 infection of primary macrophages. Since SAMHD1 was discovered as an HIV-1 restriction factor in 2011, extensive studies have revealed the mechanisms underlying SAMHD1-mediated restriction of HIV-1 replication in myeloid cells and resting CD4+ T cells. In 2018, we discovered a novel function of SAMHD1 in suppressing the innate immune response to viral infections and inflammation in macrophages. However, the underlying mechanisms of action remain unclear, representing a significant knowledge gap given the importance of macrophages in HIV-1 persistence. Our long-term goal is to define the functional roles and molecular mechanisms of cellular proteins, such as SAMHD1, in regulating innate immunity during persistent HIV-1 infection of macrophages. Our overall objective is to reveal how SAMHD1 inhibits the type I interferon (IFN-I) and NF-κB pathways in primary macrophages, acting as a multifaceted repressor of innate immune signaling induced by viral infection. IFN-I induction plays a key role in antiviral innate immunity; however, HIV-1 infection does not induce a strong IFN-I response. NF-κB is critical for HIV-1 gene transcription and immune activation, and transcriptional inhibition of viral gene expression is the main mechanism of HIV-1 latency. Thus, our central hypothesis is that SAMHD1 suppresses innate immunity to HIV-1 infection in primary macrophages by inhibiting IFN-I induction and NF-κB activation. Our three specific aims are: Aim 1. Define how SAMHD1 and IRF7 interaction inhibits IFN-I induction during HIV-1 infection; Aim 2. Examine SAMHD1 interaction with MAVS and effects on anti-HIV-1 innate immune responses; Aim 3. Investigate the mechanisms by which SAMHD1 inhibits NF-kB activation during HIV-1 infection. Our interdisciplinary studies will fill knowledge gaps to fundamentally enhance our mechanistic understanding of SAMHD1 and associated proteins in regulating HIV-1 infection, viral gene expression, immune activation, and anti-HIV-1 innate immune responses. Thus, our proposed studies of how SAMHD1 regulates immune activation and HIV-1 infection in macrophages will provide new knowledge studying viral persistence.


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 = $755,539 )
2026	2026	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	2	7/3/2026	NON-COMPETING CONTINUATION	$755,539
														Subtotal = $755,539

Issue Date FY: 2025 ( Subtotal = $769,414 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	1	7/9/2025	NEW	$769,414
														Subtotal = $769,414

Grand Total All Awards = $1,524,953

Top

All Categories

About

Search

Reports

Data Submission

Award Information

How SAMHD1 regulates HIV-1 innate immunity and viral gene expression

Award Number: R01AI189220

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: 07/09/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer