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Reassortment of Highly Pathogenic Avian Influenza: Implications for Fitness and Host Range

Award Number: R01AI201564
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2030

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Reassortment of Highly Pathogenic Avian Influenza: Implications for Fitness and Host Range - SUMMARY Highly pathogenic avian influenza viruses (HPAIVs) pose an increasing threat to both animal and human health. The rapid evolution and global dissemination of these viruses, particularly H5N1 clade 2.3.4.4b, highlight the need to elucidate drivers of cross-species transmission and adaptation. These viruses have disrupted ecosystems through mass mortality events in wild birds and marine mammals, caused devastating losses in poultry industries worldwide, established widespread circulation in US dairy cattle, and infected scores of humans exposed to affected animals. Clade 2.3.4.4b H5N1 viruses differ from ancestral H5N1 strains in the high frequency with which they are identified in mammals. While the drivers of the changing ecology of HPAIV observed with the 2.3.4.4b lineage are not clear, reassortment may play a role. This exchange of intact gene segments between co-infecting viruses can offer an evolutionary short-cut. The global expansion of 2.3.4.4b H5N1 viruses has been marked by repeated reassortment with low pathogenicity avian influenza viruses (LPAIV) across diverse avian species and multiple continents. Despite the prominence of HPAIV-LPAIV reassortment in the evolution of H5N1, we understand little of its effects on viral fitness. The potential for reassortment with human-adapted IAVs also remains unclear and is a critical factor in assessing pandemic risk. A major barrier to progress has been the lack of physiologically relevant models for assessing viral fitness across the diverse host species affected in nature. We will overcome this limitation with innovative organoid models derived from avian and mammalian species. Together with a broad panel of H5N1 isolates and state-of-the-art viral and host genetics, organoids offer an ideal platform to study viral fitness and evolution in species-specific contexts. Our overall objective is to elucidate the molecular and evolutionary pathways that enable avian IAV to cross species barriers. We will pursue this objective through three specific aims. Aim 1 will define the implications of HPAIV – LPAIV reassortment for viral fitness in novel avian and mammalian organoids. Aim 2 will elucidate constraints preventing the reassortment of the HPAIV HA and M segments. Aim 3 will using biologically contained and surrogate systems to identify evolutionary pathways enabling HPAIV adaptation to humans. By addressing the biology underpinning the extensive host range of 2.3.4.4b HPAIV and the potential for viral evolution to drive further expansion of this host range, the proposed research will offer mechanistic insight into the changing ecology of HPAIV and information critical to assess the risk of an H5N1 pandemic.


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 = $3,094,830 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	8/11/2026	NEW	$3,094,830
														Subtotal = $3,094,830

Grand Total All Awards = $3,094,830

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Reassortment of Highly Pathogenic Avian Influenza: Implications for Fitness and Host Range

Award Number: R01AI201564

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2030

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