Wednesday, January 7, 2026 1/7/2026

Regulation of SAMHD1 antiviral activity

Award Number: R01AI150455
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: 09/20/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2025

Group Awards By:

View Award Description

Regulation of SAMHD1 antiviral activity - Project Summary/Abstract Expression of the recently discovered human restriction factor SAMHD1 is responsible for the infection block imposed to lentiviruses such as HIV-1, HIV-2 and SIVmac by primary macrophages, dendritic cells and resting CD4+ T-cells. SAMHD1 blocks lentiviral infection by preventing the occurrence of reverse transcription. SAMHD1 has deoxynucleotide triphosphohydrolase (dNTPase) activity, which degrades deoxynucleotide triphosphates (dNTPs) into nucleotides and triphosphates, and this activity is required for HIV-1 restriction. However, additional studies have revealed that the dNTPase activity of SAMHD1 is not sufficient for HIV-1 restriction. Thus, an additional property of SAMHD1 is required for HIV-1 restriction. SAMHD1 interacts with nucleic acids in vitro, but the contribution of this interaction to HIV-1 restriction in vivo remains to be determined. Our preliminary data using SAMHD1 mutants indicate that nucleic acid binding is important for HIV-1 restriction. We determined the structure of SAMHD1 bound to an oligodeoxynucleotide and leveraged this structure as a tool for structure-function studies. Several amino acids form the interface between SAMHD1 and the oligodeoxynucleotide, and mutation of these residues resulted in SAMHD1 proteins that are unable to restrict HIV-1. These results suggest that the ability of SAMHD1 to interact with nucleic acids is important for HIV-1 restriction. Separate from its antiviral activity, mutations in the human SAMHD1 gene cause Aicardi- Goutières syndrome (AGS). AGS patients exhibit increased levels of type I interferon (IFN) that are believed to result from the recognition of endogenous nucleic acids by innate immune sensors. Thus, it has been suggested that the in vivo role of SAMHD1 is to prevent activation of the innate immune response by endogenous nucleic acids, and the nucleic acid binding activity of SAMHD1 has been suggested to be important for this function. Our preliminary data indicate that SAMHD1 knockout (KO) mice are resistant to herpes simplex virus 2 (HSV-2)-induced limb paralysis and death. These results suggest that SAMHD1 prevents the recognition of HSV-2 by innate immune sensors, potentially by interacting with the HSV-2 viral DNA and shielding it from detection. This strong phenotype in vivo will be used to unveil the role of SAMHD1 in innate immunity. Based on these published and preliminary results, the central hypothesis of this proposal is that the interaction of SAMHD1 with nucleic acids is important for its antiviral and innate immune functions. Our rationale is that identification of the mechanisms by which SAMHD1 modulates viral infection and innate immune responses will enable the development of novel antiviral and AGS therapies. To test our central hypothesis, we will pursue the following specific aims: 1) Determine the mechanism by which SAMHD1 inhibits HIV-1 infection, 2) Evaluate the role of SAMHD1 acetylation in SAMHD1-mediated viral restriction, and 3) Characterize the role of SAMHD1 in innate immunity.


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 = -$29,204 )
2026	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	10	12/18/2025	NON-COMPETING CONTINUATION	-$29,204
														Subtotal = -$29,204

Issue Date FY: 2024 ( Subtotal = $560,764 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	10	6/7/2024	NON-COMPETING CONTINUATION	$560,764
														Subtotal = $560,764

Issue Date FY: 2023 ( Subtotal = $560,764 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	9	7/13/2023	NON-COMPETING CONTINUATION	$560,764
														Subtotal = $560,764

Issue Date FY: 2022 ( Subtotal = $560,764 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	8	6/30/2022	NON-COMPETING CONTINUATION	$560,764
														Subtotal = $560,764

Issue Date FY: 2021 ( Subtotal = $560,665 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	002	7	6/29/2021	NON-COMPETING CONTINUATION	$560,665
2021	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	001	6	6/12/2021	COMPETING CONTINUATION	$161,819
2021	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	5	6/12/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$161,819
														Subtotal = $560,665

Issue Date FY: 2020 ( Subtotal = $576,375 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	6	6/26/2020	COMPETING CONTINUATION	$576,375
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	002	6	7/15/2020	COMPETING CONTINUATION	$0
2020	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	5	7/8/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $576,375

Issue Date FY: 2019 ( Subtotal = $440,632 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	5	8/14/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$440,632
														Subtotal = $440,632

Grand Total All Awards = $3,230,760

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of SAMHD1 antiviral activity

Award Number: R01AI150455

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: 09/20/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer