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Delineating a role for CA in HIV-1 nuclear transport to sites of integration

Award Number: R21AI145541
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: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2023

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Delineating a role for CA in HIV-1 nuclear transport to sites of integration - Project Summary HIV-1 capsid protein (CA) determines the virus nuclear entry and integration site preference. By developing novel tools to track single viral complexes that establish infection, we have recently found that point mutations in CA (N74D) influence the targeting of viral integration to the periphery as opposed to interior of the nucleus preferred by wild-type virus. A nuclear role for CA, which remains poorly appreciated, is potentially derived from the subset of CA molecules that remain associated with nuclear pre-integration complexes (PICs). We hypothesize that interaction between PIC-associated CA molecules and cellular co-factor CPSF6 directs the transport of HIV-1 to nuclear speckle regions that are rich in actively transcribing genes for integration. The scientific premise of this proposal is to characterize the CA/CPSF6 dependent nuclear HIV-1 transport to the sites of integration. We will, (1) apply live-cell imaging in combination with photoactivation techniques to visualize CPSF6 interaction with fluorescent CA-labeled PICs and their transport to sites of integration. (2) Determine a role for CPSF6/PICs interaction in the HIV-1 nuclear transport by determining diffusion coefficients of single particles in the presence of drugs and CA mutants that abrogate CA/CPSF6 interactions. (3) Develop a live-cell imaging assay to visualize the integrated vDNA, and correlate the location of PICs disappearance to integration. (4) Determine the amino acid residues in CA involved in its interaction with viral RNA or proteins in PICs and identify the binding partner of CA in vRNPs. This new direction of research will delineate a role for CA in interactions and intra-nuclear trafficking of PICs to locations of HIV-1 integration, an important step in viral life cycle that remains poorly appreciated.


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: 2024 ( Subtotal = -$6,290 )
2024	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Allergy and Infectious Diseases Research	000	2	1/22/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$6,290
														Subtotal = -$6,290

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Allergy and Infectious Diseases Research	001	2	11/5/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$111,867
2022	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	11/5/2021	NEW	-$111,867
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $231,000 )
2021	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Allergy and Infectious Diseases Research	000	2	3/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$231,000
2021	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	1	3/11/2021	NEW	$0
														Subtotal = $231,000

Issue Date FY: 2020 ( Subtotal = $195,000 )
2020	2020	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	3/2/2020	NEW	$195,000
														Subtotal = $195,000

Grand Total All Awards = $419,710

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Delineating a role for CA in HIV-1 nuclear transport to sites of integration

Award Number: R21AI145541

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: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2023

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