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We show that four arginine residues present in the NP of the 1918 H1N1 pandemic strain and early postpandemic strains were progressively substituted for by lysines between 1918 and 2009, rendering NP more susceptible to TRIM22-mediated ubiquitination. Our observations suggest that during long-term evolution of IAVs in humans, variants endowed with increased susceptibility to TRIM22 restriction emerge, highlighting the complexity of selection pressures acting on the NP.<\/jats:p>","DOI":"10.1128\/msphere.00110-18","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T12:54:40Z","timestamp":1522760080000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009"],"prefix":"10.1128","volume":"3","author":[{"given":"Isabel","family":"Pagani","sequence":"first","affiliation":[{"name":"San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Di 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