Tuesday, July 1, 2025 7/1/2025

Study of arenavirus assembly

Award Number: R01AI171426
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: 07/20/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

Group Awards By:

View Award Description

Study of arenavirus assembly - The devastating impact on public health, global economy and social stability incurred by the COVID-19 pandemic in the last two years has highlighted the importance of basic research into zoonotic pathogens. This application describes structural and functional studies into the rodent-borne human pathogen lymphocytic choriomeningitis virus (LCMV), a member of the Arenaviridae family in the Bunyavirales order. Like other members of the same family, LCMV has a negative sense, bi-segmented genome consisting of a large (L) and a small (S) segment. The L segment encodes the RNA-dependent RNA polymerase (L RdRp) protein and the multi-functional matrix protein (Z). The S segment encodes the viral nucleoprotein (NP) and the glycoprotein (GP) precursor of the glycoprotein complex (GPC) that is later cleaved into a stable signal peptide (SSP), GP1, and GP2. In the virion, nucleocapsids of NP coated L and S segments associated with the L protein are copackaged through interactions with membrane-associated Z proteins, which also interact with GPs embedded in the membrane envelope. Although structures of individual proteins from AVs have been solved by x-ray crystallography or cryo electron microscopy (cryoEM), the architectural organization of these proteins in the virion and the assembly mechanism of NP and RNA into the nucleocapsid are poorly understood. We hypothesize that NP interacts with genomic RNA segments and L RdRp to form a nucleocapsid, which is recruited to GP-decorated membrane patches through Z for budding of virions. The proposed structural and functional studies aim to test this hypothesis of LCMV virion and nucleocapsid assembly with techniques just established by our team in the collaborative studies of vesicular stomatitis virus (VSV), another negative sense RNA virus. Specifically, cryo electron tomography (cryoET) will be used to reconstruct the first 3D model of the LCMV virion at molecular resolution and atomic models of individual proteins will be fitted into the virion tomogram to establish the architectural framework of the virion and to unveil molecular interactions among GP, Z, NP and L proteins (Aim 1). Near-atomic resolution with novel sub-particle reconstruction method will be used to image fully assembled nucleocapsids consisting of NP protein and genomic RNA segment to define the protein-RNA interactions at atomic details. The nucleocapsid structure will be used to guide sub-particle reconstruction workflow and be complemented by in situ structures of nucleocapsids from virions (Aim 2). In both Aims, structure-guided functional studies will be performed to test hypotheses of assembly mechanisms of LCMV nucleocapsid and virion. Structure-function relationship relevant to viral RNA synthesis will also be explored. Overall, the anticipated results will provide new insights into the mechanism of virion assembly and viral RNA synthesis, not only for LCMV but also for Arenaviruses in general. The proposed studies harness cutting-edge technologies in structural biology and will generate new knowledge of viral structures currently unavailable to any of Arenaviruses. As such, the innovative studies shall make unique contributions by accelerating discoveries of antiviral agents and vaccines to control future AV outbreaks.


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 = $540,203 )
2025	2025	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	4	6/16/2025	NON-COMPETING CONTINUATION	$540,203
														Subtotal = $540,203

Issue Date FY: 2024 ( Subtotal = $540,203 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	3	6/20/2024	NON-COMPETING CONTINUATION	$540,203
														Subtotal = $540,203

Issue Date FY: 2023 ( Subtotal = $540,203 )
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	2	6/9/2023	NON-COMPETING CONTINUATION	$540,203
														Subtotal = $540,203

Issue Date FY: 2022 ( Subtotal = $560,443 )
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	1	7/19/2022	NEW	$560,443
														Subtotal = $560,443

Grand Total All Awards = $2,181,052

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Study of arenavirus assembly

Award Number: R01AI171426

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: 07/20/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer