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Elucidating Novel Mechanism of HIV-1 Evading APOBEC3G Antiviral Function Through Selective Viral RNA Packaging

Award Number: R21AI191964
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: 06/17/2025
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Elucidating Novel Mechanism of HIV-1 Evading APOBEC3G Antiviral Function Through Selective Viral RNA Packaging - HIV-1/AIDS can be managed with antiretroviral drugs, but treatment is lifelong, and interruption leads to viral rebound. Side effects, patient compliance, and viral resistance limit current therapy's effectiveness. To combat the rise of multidrug-resistant HIV-1, developing drugs targeting novel viral mechanisms is crucial. APOBEC3G (A3G) restricts HIV-1 replication by inhibiting viral cDNA production and inducing G-to-A hypermutations in the viral genome. While HIV-1 uses Vif to counteract A3G, evidence shows that A3G activity remains detectable in wild-type viruses. Our recent publication revealed that HIV-1 selectively packages viral genomic RNA with a lower A3G-related G to A mutation rate, suggesting a novel mechanism of HIV evades A3G antiviral function. In this application, we propose to tackle the novel mechanism of how HIV evades A3G antiviral function by preferential packaging unmutated or less-mutated genomes to its particles. We hypothesize that HIV selectively packages viral RNA with lower A3G-related G-to-A mutation rates by avoiding packaging viral RNA with mutations in crucial packaging elements like the [UUUU]:[GGAG] helical element and GGG tract. The study aims to: 1) Compare A3G-related G-to-A mutation profiles in infected cells and released virions, focusing on key packaging elements, and 2) Investigate the impact of G-to-A mutations in these regions on viral RNA packaging efficiency using mutagenesis methods. The novelty of this research lies in exploring an unexplored RNA-level mechanism of HIV evasion. Understanding this mechanism could significantly advance our knowledge of HIV pathogenesis, potentially leading to new antiretroviral therapies targeting the viral RNA packaging process and improving gene delivery vector development.


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 = $400,125 )
2025	2025	MEHARRY MEDICAL COLLEGE	1005 DR DB TODD JR BLVD	NASHVILLE	TN	37208	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	1	6/17/2025	NEW	$400,125
														Subtotal = $400,125

Grand Total All Awards = $400,125

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Elucidating Novel Mechanism of HIV-1 Evading APOBEC3G Antiviral Function Through Selective Viral RNA Packaging

Award Number: R21AI191964

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: 06/17/2025

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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