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A novel approach to pinpoint predisposed recombination regions in HIV for a global profile of HIV recombinants' occurrence and evolution

Award Number: R21AI176947
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: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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A novel approach to pinpoint predisposed recombination regions in HIV for a global profile of HIV recombinants' occurrence and evolution - Project Summary/Abstract Occurring more frequent than point mutations, the recombination events in HIV have resulted in epidemiologically important founder strains in various geographic regions and contribute to at least 20-30% of global HIV infections. However, after 33 years of recognizing HIV recombination, two critical questions still remain elusive as to how HIV recombination events have occurred and how to predict emerging recombinant clusters to better inform public health decision making. Based on nearly 20 years of HIV experience, we believe that both questions relate to the flaws inherent in the current classification system for HIV recombinant families (CRFs), which has inadequately appreciated the rapid virus evolution within and between recombinant families. As a result, this static definition of CRFs not only creates a small-sample-size problem for most CRFs, but also makes it difficult to track viral evolution in a dynamic means; while both issues are essential for public health surveillance and for improved vaccine and antivirals design targeting HIV recombinants. In this proposed study, our objectives are to: 1) strategically fulfill the inadequate and missing CRF information to overcome the small- sample-size problem created by the CRF definition, and 2) provide a global profile along the HIV genome about HIV’s recombination occurrence and evolution via pinpointing HIV predisposed recombination regions based on the enriched CRF information. Our central hypothesis is that the inadequate and missing CRF information, which accounts for the limited sample size for most CRFs and the lack of a dynamic view of CRFs, can be strategically fulfilled by adding information from HIV fragment sequences (i.e., non-full-length sequences) that consist of over 90% of all published HIV data deposited in GenBank. Our hypothesis is based on several important lines of evidence, including results from our studies. Our rationale for this proposed study is that fulfilling the inadequate and missing CRF information will increase our capabilities in the surveillance and tracking of existing HIV recombinants and for improved prediction of emerging HIV recombinants’ clusters. Leveraged by our nearly 20 years of experience in HIV data mining, statistical method development, statistical machine learning, and statistical genetics, we will develop and validate two new methods in three Aims. By the end of this proposed project, we expect to obtain new methods and new findings to advance our understanding of the CRFs (e.g., recombination mechanisms and evolution) and for improved public health surveillance for existing and emerging CRF clusters. Finally, our methods and results will be released for free to facilitate other viruses’ research in recombination.


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 = $0 )
2025	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	12/11/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $197,008 )
2024	2024	TRIAD NATIONAL SECURITY, LLC	505 KING AVE	COLUMBUS	OH	43201	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	2	8/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$197,008
2024	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	8/9/2024	NEW	$0
														Subtotal = $197,008

Issue Date FY: 2023 ( Subtotal = $188,750 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	5/30/2023	NEW	$188,750
														Subtotal = $188,750

Grand Total All Awards = $385,758

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A novel approach to pinpoint predisposed recombination regions in HIV for a global profile of HIV recombinants' occurrence and evolution

Award Number: R21AI176947

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: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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