Genetic resilience or resistance in poultry against avian influenza virus: mirage or reality

Authors: Chen, Paula; White, Stephen; Walker, Lianna; Kapczynski, Darrell; Suarez, David

Submitted to: Journal of Virology
Publication Type: Review Article
Publication Acceptance Date: 6/15/2025
Publication Date: 6/30/2025
Citation: Chen, P.R., White, S.N., Walker, L.R., Kapczynski, D.R., Suarez, D.L. 2025. Genetic resilience or resistance in poultry against avian influenza virus: mirage or reality. Journal of Virology. 22;99(7). https://doi.org/10.1128/jvi.00820-25.
DOI: https://doi.org/10.1128/jvi.00820-25

Interpretive Summary: Highly pathogenic avian influenza virus is an important disease in both poultry and mammals. The U.S. is currently experiencing the largest outbreak of the disease we have ever experienced, and because the virus is in wild birds, it will be difficult to eliminate the virus exposure. Alternative methods for prevention of the disease are being considered, and an ideal solution would be to have poultry completely resistant to being infected. However, there has been no identification of poultry that have complete natural resistance to the disease. There is some research that has identified some genes that may reduce the clinical disease, but more research needs to be done to see if these genes provide enough protection from disease and doesn't negatively affect the growth of the birds. An alternative approach is to genetically engineer birds by deleting host genes important for influenza growth or insert genes from other sources that may reduce or block viral growth. Several studies have identified possible genetic changes, but like with the natural resistance genes, more work needs to be done to see if these changes can protect against influenza and not reduce the productivity of the chicken. A review of host resilience and resistance research highlights where we currently are and possible paths forward.

Technical Abstract: The unprecedented global spread of highly pathogenic avian influenza (HPAI) in wild birds, poultry, and mammalian species has challenged our control efforts. Alternative approaches to limit avian influenza virus (AIV) include development of resilient or resistant chickens. Genetically resilient birds may become infected but can overcome disease, whereas resistant birds prevent virus attachment or entry. The most intensively studied host gene is myxovirus-resistance (Mx), which is expressed via the interferon pathway. Both sensitive and resistant chicken Mx genotypes have been described, but this only provides limited resilience. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been demonstrated as a host cofactor in AIV replication via interaction with viral polymerase. Small nucleotide changes within this gene have demonstrated some promise for establishment of disease resilience. Certain MHC-defined genetic chicken lines have demonstrated increased resilience with higher innate immune responses, but HPAI infected birds still have high morbidity and mortality. Alternatively, gene edited or transgenic chickens have had some success in increasing resilience. This strategy allows flexibility to include foreign genes, modification of existing genes, or combined approaches to block critical steps in the viral life cycle. Some candidate genes include solute carrier 35A1 (SLC35A1), retinoic acid-inducible gene I (RIGI), and toll-like receptor 3 and 7 (TLR3/7), but animal testing needs to be conducted. Furthermore, existing hurdles for technology transfer to commercial application from either naturally occurring resistance genes or foreign genes remain high and will require acceptance by both the poultry industry and consumers.