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Cryo-ET Guided Single Particle Reconstruction of HIV

Award Number: R21AI148328
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: 08/21/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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Cryo-ET Guided Single Particle Reconstruction of HIV - ABSTRACT The atomic resolution structures of the human immunodeficiency virus type 1 (HIV-1) Gag lattice have revealed critical molecular contacts that stabilize the HIV-1 immature particle structure and have informed HIV- 1 proteolytic cleavages and Gag lattice disassembly. In order to gain a fundamental understanding of retrovirus assembly and maturation, atomic resolution maps of immature particles for the Orthoretrovirinae are required. Here we propose a strategy, i.e., cryo-electron tomography (cryo-ET) guided single particle reconstruction (SPR), to achieve atomic resolution reconstruction maps of retrovirus immature particles. We will use human immunodeficiency virus type 2 (HIV-2) as the basis for implementation of this image processing strategy. We will then apply the method to the study of other retrovirus immature particle structures, e.g., human T-cell leukemia virus type 1 (HTLV-1), and conduct comparative studies about the conservation of key molecular interactions in HIV-1, HIV-2 and HTLV-1 Gag lattice structures. We will also apply this approach for the study of membrane anchored HIV-1 envelope protein structure. This proposed hybrid image processing method takes advantage of the strengths of both cryo-EM imaging methods (i.e. cryo-ET and SPR) and overcomes the computation challenges that each method bears when processing images of retrovirus immature particles.


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 = $0 )
2024	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	2	4/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $193,750 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	2	7/22/2021	NON-COMPETING CONTINUATION	$193,750
														Subtotal = $193,750

Issue Date FY: 2020 ( Subtotal = $231,125 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	1	8/21/2020	NEW	$231,125
														Subtotal = $231,125

Grand Total All Awards = $424,875

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Cryo-ET Guided Single Particle Reconstruction of HIV

Award Number: R21AI148328

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: 08/21/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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