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Drivers of the beneficial effects of influenza A virus co-infection

Award Number: F31AI189070
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2025
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Drivers of the beneficial effects of influenza A virus co-infection - PROJECT SUMMARY/ABSTRACT Influenza A viruses (IAVs) cause several million infections each year in the Unites States alone and have significant health, economic, and ecological impacts, despite widespread pre-exposure, vaccination, and surveillance efforts. Given the substantial, recurring impact of IAV on human health, it is essential to better understand the fundamental processes shaping viral propagation. Throughout viral infection, the number of virions infecting individual cells varies over space and time. Consequently, multiple infection is a common feature of within-host viral expansion. For IAV, homologous cellular co-infection has the potential to increase viral replication and progeny production, suggesting that multiple infection increases the chances of completing the infection cycle successfully. This dynamic, in which groups of viruses are more often successful than single viruses, is in line with the ecological concept of positive density-dependence. However, the specific viral processes that give rise to these beneficial effects of multiple infection are unknown. Therefore, I hypothesize that IAVs exhibit positive density-dependence during essential steps of the early viral life cycle and that this dependence is heightened under an antiviral state. To test this hypothesis, I will use influenza A/Netherlands/602/2009 (H1N1) virus (NL/09) to generate a panel of viral variants that are deficient in core processes of the early viral life cycle and determine the extent to which the fitness effects of the introduced mutations vary with multiple infection. In addition to being is a well-studied virus, NL/09 exhibits an intrinsically low reliance on multiple infection. Using this virus will allow us to identify positive density-dependent phenotypes conferred by the introduced mutations. In Aim 1, I will evaluate the density-dependence of discrete viral functions by defining the relationships between viral density and the fitness effects of mutations that target those functions. Each mutational fitness effect will be evaluated using the Lowen lab’s VAR1-VAR2 system, which comprises two viruses differing by a single synonymous mutation introduced into each gene segment of the VAR2 virus. These synonymous mutations allow measurement of the benefit of multiple infection on the replication of the focal virus. In Aim 2, I will use viral genetic barcodes to investigate how the density-dependence of specific viral processes interfaces with the replicative success rate of incoming viral genomes. Each variant virus will possess a distinct barcode region in the neuraminidase (NA) segment with twelve bi-allelic sites, resulting in a total of 4096 unique genotypes. I will utilize genetic barcodes to monitor the fate of individual barcodes within the population and to detect changes in replicative success rate within a given cell and the viral progeny produced. For both aims, I will further examine positive density-dependent phenotypes under an induced antiviral state. The findings of this project will strengthen our fundamental understanding of the impact of multiple infection among IAVs, while elucidating potentially important and underappreciated determinants of infection outcomes. This knowledge can contribute to the development of improved infection control and mitigation strategies.


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 = $49,538 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	12/29/2025	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $49,538

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	1	12/27/2024	NEW	$0
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	1	7/29/2025	NEW	$564
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	12/27/2024	NEW	$48,974
														Subtotal = $49,538

Grand Total All Awards = $99,076

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Drivers of the beneficial effects of influenza A virus co-infection

Award Number: F31AI189070

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2025

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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