Neumann, G., Eisfeld Amie, J. & Kawaoka, Y. Viral factors underlying the pandemic potential of influenza viruses. Microbiol. Mol. Biol. Rev. 89, e0006624 (2025).
Taubenberger, J. K. & Kash, J. C. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 7, 440–451 (2010).
Ma, W. Swine influenza virus: current status and challenge. Virus Res. 288, 198118 (2020).
Veldhuis Kroeze, E. J. B. & Kuiken, T. in Animal Influenza 2nd edn (ed Swayne, D. E.) Ch. 23 (John Wiley & Sons, Inc., 2016).
Long, J. S., Mistry, B., Haslam, S. M. & Barclay, W. S. Host and viral determinants of influenza A virus species specificity. Nat. Rev. Microbiol. 17, 67–81 (2019).
Peacock, T. P. et al. The global H5N1 influenza panzootic in mammals. Nature 637, 304–313 (2025).
Lam, T. T.-Y. et al. Dissemination, divergence and establishment of H7N9 influenza viruses in China. Nature 522, 102–105 (2015).
Tan, X. et al. A case of human infection by H3N8 influenza virus. Emerg. Microbes Infect. 11, 2214–2217 (2022).
Nidra, F. Y., Monir, M. B. & Dewan, S. M. R. Avian influenza A (H5N1) outbreak 2024 in Cambodia: worries over the possible spread of the virus to other Asian nations and the strategic outlook for its control. Environ. Health Insights 18, 11786302241246453 (2024).
Cox, N. J., Trock, S. C. & Burke, S. A. in Influenza Pathogenesis and Control Vol. I (eds Compans, R. & Oldstone, M.) Ch. 5 (Springer, 2014).
Tool for Influenza Pandemic Risk Assessment (TIPRA) (World Health Organization, 2016).
Honce, R. & Schultz-Cherry, S. Recipe for zoonosis: how influenza virus leaps into human circulation. Cell Host Microbe 28, 506–508 (2020).
Greenbaum, B. D., Levine, A. J., Bhanot, G. & Rabadan, R. Patterns of evolution and host gene mimicry in influenza and other RNA viruses. PLoS Pathog. 4, e1000079 (2008).
Gu, H., Fan, R. L. Y., Wang, D. & Poon, L. L. M. Dinucleotide evolutionary dynamics in influenza A virus. Virus Evol. 5, vez038 (2019).
Gaunt, E. et al. Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection. Elife 5, e12735 (2016).
Chang, C.-C. & Lin, C.-J. LIBSVM: a library for support vector machines. ACM Trans. Intell. Syst. Technol. 2, 27 (2011).
Anderson, T. K. et al. A phylogeny-based global nomenclature system and automated annotation tool for H1 hemagglutinin genes from swine influenza A viruses. mSphere https://doi.org/10.1128/msphere.00275-16 (2016).
Voorhees, I. E. H. et al. Spread of canine influenza A (H3N2) virus, United States. Emerg. Infect. Dis. 23, 1950–1957 (2017).
Sharp, P. M. & Li, W.-H. The codon adaptation index—a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 15, 1281–1295 (1987).
Brower-Sinning, R. et al. The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus. Genome Biol. 10, R18 (2009).
Shimizu, S., Hoyer, P. O., Hyvärinen, A., Kerminen, A. & Jordan, M. A linear non-Gaussian acyclic model for causal discovery. J. Mach. Learn. Res. 7, 2003–2030 (2006).
Cheng, X. et al. CpG usage in RNA viruses: data and hypotheses. PLoS ONE 8, e74109 (2013).
Vieira, V. C. & Soares, M. A. The role of cytidine deaminases on innate immune responses against human viral infections. BioMed Res. Int. 2013, 683095 (2013).
Su, W. et al. Ancestral sequence reconstruction pinpoints adaptations that enable avian influenza virus transmission in pigs. Nat. Microbiol. 6, 1455–1465 (2021).
Caserta, L. C. et al. Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature 634, 669–676 (2024).
Puryear, W. et al. Highly pathogenic avian influenza A (H5N1) virus outbreak in New England seals, United States. Emerg. Infect. Dis. 29, 786–791 (2023).
Uhart, M. M. et al. Epidemiological data of an influenza A/H5N1 outbreak in elephant seals in Argentina indicates mammal-to-mammal transmission. Nat. Commun. 15, 9516 (2024).
Agüero, M. et al. Highly pathogenic avian influenza A (H5N1) virus infection in farmed minks, Spain, October 2022. Euro Surveill. 28, 2300001 (2023).
Fusaro, A. et al. High pathogenic avian influenza A (H5) viruses of clade 2.3.4.4b in Europe—why trends of virus evolution are more difficult to predict. Virus Evol. 10, veae027 (2024).
Kareinen, L. et al. Highly pathogenic avian influenza A (H5N1) virus infections on fur farms connected to mass mortalities of black-headed gulls, Finland, July to October 2023. Euro Surveill. 29, 2400063 (2024).
Finkelstein, D. B. et al. Persistent host markers in pandemic and H5N1 influenza viruses. J. Virol. 81, 10292–10299 (2007).
Chun, J. Influenza including its infection among pigs. Natl Med. J. China 5, 34–44 (1919).
Jones, J. C. et al. Risk assessment of H2N2 influenza viruses from the avian reservoir. J. Virol. 88, 1175–1188 (2014).
Harkness, W., Schild, G. C., Lamont, P. H. & Brand, C. M. Studies on relationships between human and porcine influenza. 1. Serological evidence of infection in swine in Great Britain with an influenza A virus antigenically like human Hong Kong-68 virus. Bull. World Health Organ. 46, 709–719 (1972).
Furmanski, M. & Murcia, P. R. Did horses act as intermediate hosts that facilitated the emergence of 1918 pandemic influenza? J. Infect. Dis. 232, 521–524 (2025).
Meneu, L. et al. Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus. Science 387, eadm9466 (2025).
Galtier, N. & Lobry, J. R. Relationships between genomic G+C content, RNA secondary structures, and optimal growth temperature in prokaryotes. J. Mol. Evol. 44, 632–636 (1997).
Bisht, K. & te Velthuis, A. J. W. Decoding the role of temperature in RNA virus infections. mBio 13, e0202122 (2022).
Li, Y. et al. Low RNA stability signifies increased post-transcriptional regulation of cell identity genes. Nucleic Acids Res. 51, 6020–6038 (2023).
Le Sage, V., Campbell, A. J., Reed, D. S., Duprex, W. P. & Lakdawala, S. S. Persistence of influenza H5N1 and H1N1 viruses in unpasteurized milk on milking unit surfaces. Emerg. Infect. Dis. 30, 1721–1723 (2024).
Nguyen, T.-Q. et al. Emergence and interstate spread of highly pathogenic avian influenza A (H5N1) in dairy cattle in the United States. Science 388, eadq0900 (2025).
Plaza, P. I. et al. Pacific and Atlantic sea lion mortality caused by highly pathogenic avian influenza A (H5N1) in South America. Travel Med. Infect. Dis. 59, 102712 (2024).
Sun, H. et al. Mink is a highly susceptible host species to circulating human and avian influenza viruses. Emerg. Microbes Infect. 10, 472–480 (2021).
Restori, K. H. et al. Risk assessment of a highly pathogenic H5N1 influenza virus from mink. Nat. Commun. 15, 4112 (2024).
Lindh, E. et al. Highly pathogenic avian influenza A (H5N1) virus infection on multiple fur farms in the South and Central Ostrobothnia regions of Finland, July 2023. Euro Surveill. 28, 2300400 (2023).
Pepin, K. M., Lass, S., Pulliam, J. R. C., Read, A. F. & Lloyd-Smith, J. O. Identifying genetic markers of adaptation for surveillance of viral host jumps. Nat. Rev. Microbiol. 8, 802–813 (2010).
Gu, C. et al. A human isolate of bovine H5N1 is transmissible and lethal in animal models. Nature 636, 711–718 (2024).
Eisfeld, A. J. et al. Pathogenicity and transmissibility of bovine H5N1 influenza virus. Nature 633, 426–432 (2024).
Shu, Y. & McCauley, J. GISAID: global initiative on sharing all influenza data—from vision to reality. Euro Surveill. 22, 30494 (2017).
Heiny, A. T. et al. Evolutionarily conserved protein sequences of influenza A viruses, avian and human, as vaccine targets. PLoS ONE 2, e1190 (2007).
Ye, Y. et al. GLProbs: aligning multiple sequences adaptively. IEEE/ACM Trans. Comput. Biol. Bioinform. 12, 67–78 (2015).
Sievers, F. & Higgins, D. G. Clustal Omega for making accurate alignments of many protein sequences. Protein Sci. 27, 135–145 (2018).
Suyama, M., Torrents, D. & Bork, P. PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucleic Acids Res. 34, W609–W612 (2006).
Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2—approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490 (2010).
Paradis, E. & Schliep, K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 35, 526–528 (2019).
Ishikawa, S. A., Zhukova, A., Iwasaki, W. & Gascuel, O. A fast likelihood method to reconstruct and visualize ancestral scenarios. Mol. Biol. Evol. 36, 2069–2085 (2019).
Ye, Y. et al. F1ALA: ultrafast and memory-efficient ancestral lineage annotation applied to the huge SARS-CoV-2 phylogeny. Virus Evol. 10, veae056 (2024).
Ye, Y. et al. Robust expansion of phylogeny for fast-growing genome sequence data. PLoS Comput. Biol. 20, e1011871 (2024).
Nakamura, Y., Gojobori, T. & Ikemura, T. Codon usage tabulated from international DNA sequence databases: status for the year 2000. Nucleic Acids Res. 28, 292–292 (2000).
Lorenz, R. et al. ViennaRNA package 2.0. Algorithms Mol. Biol. 6, 26 (2011).
Chen, Y.-W. & Lin, C.-J. Combining SVMs with various feature selection strategies. in Feature Extraction. Studies in Fuzziness and Soft Computing Vol. 207 (eds Guyon, I. et al.) 315–324 (Springer, 2006).
Lycett, S. et al. Highly pathogenic avian influenza and its complex patterns of reassortment. In Epidemics 9: 9th International Conference on Infectious Disease Dynamics P3.092 (SSRN, 2024).
Youk, S. et al. H5N1 highly pathogenic avian influenza clade 2.3.4.4b in wild and domestic birds: introductions into the United States and reassortments, December 2021–April 2022. Virology 587, 109860 (2023).
Yu, G., Smith, D. K., Zhu, H., Guan, Y. & Lam, T. T.-Y. ggtree: an R package for visualization and annotation of phylogenetic trees with their covariates and other associated data. Methods Ecol. Evol. 8, 28–36 (2017).
Minh, B. Q. et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol. Biol. Evol. 37, 1530–1534 (2020).
Suttie, A. et al. Inventory of molecular markers affecting biological characteristics of avian influenza A viruses. Virus Genes 55, 739–768 (2019).
Mertens, E. et al. Evaluation of phenotypic markers in full genome sequences of avian influenza isolates from California. Comp. Immunol. Microbiol. Infect. Dis. 36, 521–536 (2013).
WHO H5N1 Genetic Changes Inventory: A Tool for International Surveillance (CDC, 2015).
Suchard, M. A. et al. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol. 4, vey016 (2018).
Gill, M. S. et al. Improving Bayesian population dynamics inference: a coalescent-based model for multiple loci. Mol. Biol. Evol. 30, 713–724 (2013).
Rambaut, A., Drummond, A. J., Xie, D., Baele, G. & Suchard, M. A. Posterior summarization in Bayesian phylogenetics using Tracer 1.7. Syst. Biol. 67, 901–904 (2018).
Bielejec, F. et al. SpreaD3: interactive visualization of spatiotemporal history and trait evolutionary processes. Mol. Biol. Evol. 33, 2167–2169 (2016).