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Mapping spatiotemporal dynamics during enterovirus infection across cells and tissues

Award Number: R01AI169460
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: 03/10/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Mapping spatiotemporal dynamics during enterovirus infection across cells and tissues - Project Summary Human enterovirus (HEV) infections primarily affect infant and adolescent populations, causing a wide range of clinical manifestations that commonly include respiratory illness and mucocutaneous lesions, or hand, foot and mouth disease. In some cases, the infection is life- threatening. The clinical manifestations are a function of their tropism. For example, some HEVs, including EV-A71 and EV-D68, are associated with serious neurological symptoms due to invasion and damage of central nervous tissues. Others, such CVB3, are implicated in respiratory symptoms and cardiomyopathy. This proposal aims to take an integrative approach to understand how tissues, and cells within these tissues, respond to infection by CVB3 and the emerging pathogens EV-D68 and EV-A71. We will determine the temporal and spatial dynamics of HEV infection using recent advances in genomics: (i) We will profile single-cell transcriptomes to quantify viral replication levels and the host response to infection across cells and tissues over the course of infection. (ii) Given that intra-host adaptation appears to be important in infection, in parallel, we will map the mutational spectrum of the replicating viruses using a novel ultra-deep sequencing approach. We will use new innovative technologies, such as ultra-deep virus population sequencing, deep learning and single-cell analysis to increase our basic understanding of the pathogenesis of enteroviruses A, B and D. Finally, given that innate immunity is a major determinant of tissue tropism, we will use mice with deletions of specific type-I IFN subtypes to determine the significance of interferon diversity in controlling HEV infections. These data will enable us to determine cell types that HEVs infect, the response that the host mounts against them in each cell and tissue, and the viral mutants that emerge in different tissues. Understanding pathogenesis is critically needed for developing effective and broadly-acting countermeasures and to inform the development of effective and broad-spectrum vaccines and antiviral compounds.


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	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	3	4/21/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $995,789 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	3	6/11/2024	SUPPLEMENT FOR EXPANSION	$147,486
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	3	4/2/2024	NON-COMPETING CONTINUATION	$848,303
														Subtotal = $995,789

Issue Date FY: 2023 ( Subtotal = $946,627 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	2	2/16/2023	NON-COMPETING CONTINUATION	$848,303
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	2	8/31/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	2	8/11/2023	SUPPLEMENT FOR EXPANSION	$98,324
														Subtotal = $946,627

Issue Date FY: 2022 ( Subtotal = $868,678 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	1	3/10/2022	NEW	$868,678
														Subtotal = $868,678

Grand Total All Awards = $2,811,094

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Mapping spatiotemporal dynamics during enterovirus infection across cells and tissues

Award Number: R01AI169460

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: 03/10/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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