Genetic immunity to avian influenza: new FFAR–Iowa State–CSIRO project

Highly pathogenic avian influenza (HPAI) continues to pose a structural threat to the U.S. poultry industry, causing billions of dollars in economic losses, production disruptions and increased costs along the supply chain. Alongside biosecurity measures and vaccination strategies, there is growing interest in approaches that leverage the host’s genetic response to reduce the impact of influenza viruses.

A $300,000 ROAR grant for H5N1 and H7N9

The Foundation for Food & Agriculture Research (FFAR), in collaboration with Iowa State University and the Commonwealth Scientific and Industrial Research Organisation (CSIRO), has awarded $300,000 through the Rapid Outcomes from Agricultural Research (ROAR) program. The goal is to identify genetic factors in birds that modulate the host response to H5N1 and H7N9 viruses, helping to unravel the molecular mechanisms involved in the response to infection and to pinpoint potential targets for future control strategies.pubmed.ncbi.nlm.nih+2

Although global attention is currently focused primarily on H5N1, H7N9 also remains an avian influenza virus of particular scientific interest due to its zoonotic potential and is being studied to better understand the mechanisms of the host immune response.

FFAR, USDA and protecting profitability

The project falls under FFAR’s research priority area “Increasing Profitability of Farmers and Ranchers,” which aims to develop innovative tools to protect poultry production in both the short and long term. Established under the 2014 Farm Bill, FFAR builds public–private partnerships to fund high‑impact research on key agri‑food challenges, matching federal funds with private investment through programs such as ROAR, designed to rapidly support research projects addressing emerging issues in the agricultural sector.

Scientific focus: host genes and immune response

The project, led by Joaquín Caceres, assistant professor in the Department of Veterinary Microbiology and Preventive Medicine at Iowa State University’s College of Veterinary Medicine, uses advanced genomic tools and experimental models to study how birds respond to H5N1 and H7N9 infections. The team aims to identify genes and molecular pathways involved in the host response to infection, with the goal of improving our understanding of the mechanisms that determine susceptibility or resilience to influenza viruses. Over time, the knowledge generated may contribute to the development of new control strategies, including genetic selection of more resilient animals and, more broadly, the identification of potential targets for future therapeutic or vaccine applications.pubmed.

Resilience and resistance: insights from the literature

A recent review by the USDA‑ARS group distinguishes between genetic “resilience” and “resistance”: resilient animals can become infected but limit clinical severity and recover more quickly, whereas resistant animals impede virus entry or replication, significantly reducing infectivity and transmission. Among the most studied host genes are ANP32A, an essential cofactor for influenza polymerase; SLC35A1, involved in the synthesis of sialic‑acid–containing receptors; and the innate immune receptors TLR3 and TLR7. The Mx (myxovirus resistance) gene has also been proposed as a possible antiviral factor, although its protective role in chickens remains debated in the scientific literature. Another key point of interest is RIG‑I, an important sensor of antiviral immunity present in several avian species, such as ducks, but absent in the domestic chicken, a feature that may contribute to inter‑species differences in susceptibility to influenza viruses.

Genetic approaches for greater resilience to avian influenza

A further review authored by CSIRO researchers highlights how the development of chicken lines resilient to avian influenza is emerging as a promising long‑term management strategy, complementary to vaccination and biosecurity. The authors emphasize the potential of intracellular restriction factors, large‑scale genomic screening to identify new candidate genes, and proof‑of‑concept studies based on transgenesis and gene editing to modify antiviral genes without compromising production performance.

From the lab to commercial genetics

A dedicated review on commercial genetic selection for disease resistance shows how poultry breeding companies are increasingly integrating tools such as genome‑wide association studies (GWAS), molecular markers and genomic selection to improve animal resilience and robustness, thereby reducing reliance on pharmaceutical treatments. The application of gene editing to avian influenza—for example through modifications of ANP32A aimed at weakening its interaction with viral polymerase—remains confined to experimental research and is not yet used in commercial populations, due both to high development costs and to regulatory and consumer‑acceptance challenges.

Implications for HPAI control

The research line supported by FFAR aims to expand the “toolbox” available for HPAI control by complementing virus‑directed strategies, such as vaccines and biosecurity, with host‑directed approaches grounded in an understanding of the host’s genetic mechanisms. Because host genetic factors are generally more stable than influenza virus genomes, such approaches could offer new opportunities to strengthen the resilience of poultry production systems.

Looking ahead, the identification of genetic markers associated with improved control of infection and reduced viral shedding could be integrated into selection programs for major commercial lines, contributing to the development of more resilient flocks and greater stability across the global poultry value chain.