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Host dependence of influenza A virus spatio-temporal dynamics

Award Number: R01AI127799
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: 12/05/2016
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Host dependence of influenza A virus spatio-temporal dynamics - SUMMARY Influenza A viruses (FLUAVs) circulate in a wide range of avian and mammalian hosts. Specific viral lineages are host restricted and tend to transmit among individuals of one or a small number of related species. Host range expansion is relatively common, however, with spillover between species occasionally giving rise to novel lineages and – with them – novel outbreaks. Owing to their implications for human and animal health, the drivers of and barriers to viral host range expansion garner significant attention. Much of this attention focuses at molecular and cellular levels, however, leaving a gap in understanding the impact of host differences on virus- host interactions that play out within tissues, between tissues and between individuals. These interactions are complex and multi-faceted. They are also highly consequential: they shape viral populations, define disease outcomes, and determine the potential for onward transmission. Thus, host specific differences in viral population structure and dynamics represent a major uncharted area of virology. To address this gap, we will examine FLUAV dynamics in a diverse set of host species, including multiple natural hosts, deploying state of the art viral genetics and next generation sequencing approaches to collect detailed spatial and temporal information as viral populations expand within hosts and transmit between them. Our overarching hypothesis is that viral populations are shaped predominantly by tissue tropism and transmission routes, such that parallels will be seen among disparate hosts in which FLUAV has a respiratory tropism, but categorically different viral dynamics will be apparent where FLUAV has enteric tropism or spreads systemically. To test this hypothesis, we will monitor barcoded virus libraries in ferrets, swine, mallards, chickens and quail. Systematic biopsy-based tissue sampling will be used to collect spatially resolved information while serial swab-based sampling will be used to collect longitudinal data. Results will enable a deep understanding of viral dissemination, a key driver of pathogenesis, and will define the extent to which stochastic processes shape viral evolutionary dynamics both within hosts and between hosts during transmission. Importantly, comparison of the patterns observed across species will reveal which of these aspects of FLUAV biology are common across hosts, and which are distinct, in turn furnishing novel insight into the virological and evolutionary consequences of host species transitions.


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: 2026 ( Subtotal = $655,556 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	7	12/4/2025	NON-COMPETING CONTINUATION	$655,556
														Subtotal = $655,556

Issue Date FY: 2025 ( Subtotal = $670,000 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	6	5/15/2025	COMPETING CONTINUATION	$0
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	6	11/22/2024	COMPETING CONTINUATION	$670,000
														Subtotal = $670,000

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	10/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	3/28/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $544,178 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	11/27/2020	NON-COMPETING CONTINUATION	$544,178
2021	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	4	1/8/2021	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $544,178

Issue Date FY: 2020 ( Subtotal = $760,694 )
2020	2020	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	11/20/2019	NON-COMPETING CONTINUATION	$633,061
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	4	5/28/2020	SUPPLEMENT FOR EXPANSION	$127,633
														Subtotal = $760,694

Issue Date FY: 2019 ( Subtotal = $616,281 )
2019	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	11/15/2018	NON-COMPETING CONTINUATION	$616,281
														Subtotal = $616,281

Issue Date FY: 2018 ( Subtotal = $619,566 )
2018	2018	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	11/20/2017	NON-COMPETING CONTINUATION	$619,566
														Subtotal = $619,566

Issue Date FY: 2017 ( Subtotal = $627,494 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	12/2/2016	NEW	$627,494
														Subtotal = $627,494

Grand Total All Awards = $4,493,769

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Host dependence of influenza A virus spatio-temporal dynamics

Award Number: R01AI127799

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: 12/05/2016

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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