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Structure of HIV Rev response element

Award Number: R21AI181621
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: 05/23/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Structure of HIV Rev response element - Abstract Human immunodeficiency virus (HIV) targets the immune cells and weakens our defense against many infections and cancer. If not treated, HIV can progress into acquired immunodeficiency syndrome (AIDS). Although antiretroviral therapy is a key component in HIV treatment and prevention, the rapid development of drug-resistant HIV strains limits the selection of effective therapies available for patients. Thus, there is an urgent need to identify alternative viral targets for inhibition. An essential yet poorly understood step in HIV replication is Rev-response element (RRE) mediated nuclear export of the viral RNAs. During HIV infection, partially spliced and unspliced viral RNAs need to be exported from the host cell nucleus to the cytoplasm to synthesize viral proteins and assemble virions. Since incompletely spliced transcripts cannot be exported by the nuclear export system, HIV uses a specific RNA sequence Rev Response Element (RRE) that are present in the incompletely spliced viral RNAs that viral Rev protein specifically recognizes. Multimeric Rev proteins bind to the RRE structure and recruit the nuclear export complex for cytoplasmic translocation of the viral RNAs. However, the architecture of the highly specific RRE-Rev multimeric complex is unknown, largely due to the lack of the RRE structure. We will use RNA-scaffold approaches that we developed and determine the structures of the initial high-affinity Rev binding site of RRE (stem-loop II) and the full-length RRE. We will further characterize the molecular interactions between RRE and Rev. Understanding the contribution of RNA structure that drive Rev oligomerization will aid development of HIV therapeutics that target RRE and Rev interaction.


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: 2025 ( Subtotal = $192,181 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Allergy and Infectious Diseases Research	000	2	3/11/2025	NON-COMPETING CONTINUATION	$192,181
														Subtotal = $192,181

Issue Date FY: 2024 ( Subtotal = $237,750 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$23,775
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Allergy and Infectious Diseases Research	000	1	5/23/2024	NEW	$213,975
														Subtotal = $237,750

Grand Total All Awards = $429,931

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Structure of HIV Rev response element

Award Number: R21AI181621

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: 05/23/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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