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00925njm 22002777a 4500 dc Muñoz Moreno, Raquel author Martínez Romero, Carles author Blanco Melo, Daniel author Forst, Christian V. author Nachbagauer, Raffael author Benitez, Asiel Arturo author Mena, Ignacio author Aslam, Sadaf author Balasubramaniam, Vinod author Lee, Ilseob author Panis, Maryline author Ayllón Barasoain, Juan author Sachs, David author Park, Man-Seong author Krammer, Florian author tenOever, Benjamin R. author García Sastre, Adolfo author 2019 Influenza A viruses (IAVs) have a remarkable tropism in their ability to circulate in both mammalian and avian species. The IAV NS1 protein is a multifunctional virulence factor that inhibits the type I interferon host response through a myriad of mechanisms. How NS1 has evolved to enable this remarkable property across species and its specific impact in the overall replication, pathogenicity, and host preference remain unknown. Here we analyze the NS1 evolutionary landscape and host tropism using a barcoded library of recombinant IAVs. Results show a surprisingly great variety of NS1 phenotypes according to their ability to replicate in different hosts. The IAV NS1 genes appear to have taken diverse and random evolutionary pathways within their multiple phylogenetic lineages. In summary, the high evolutionary plasticity of this viral protein underscores the ability of IAVs to adapt to multiple hosts and aids in our understanding of its global prevalence. 2211-1247 http://hdl.handle.net/10259/7994 10.1016/j.celrep.2019.11.070 Influenza virus Orthomyxovirus NS1 evolution IFN response Innate immunity Barcoded library Viral Fitness Landscapes in Diverse Host Species Reveal Multiple Evolutionary Lines for the NS1 Gene of Influenza A Viruses