{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:18:36Z","timestamp":1790680716082,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>PB1-F2 is an accessory protein of most human, avian, swine, equine, and canine influenza A viruses (IAVs). Although it is dispensable for virus replication and growth, it plays significant roles in pathogenesis by interfering with the host innate immune response, inducing death in immune and epithelial cells, altering inflammatory responses, and promoting secondary bacterial pneumonia. The effects of PB1-F2 differ between virus strains and host species. This can at least partially be explained by the presence of multiple PB1-F2 sequence variants, including premature stop codons that lead to the expression of truncated PB1-F2 proteins of different lengths and specific virulence-associated residues that enhance susceptibility to bacterial superinfection. Although there has been a tendency for human seasonal IAV to gradually reduce the number of virulence-associated residues, zoonotic IAVs contain a reservoir of PB1-F2 proteins with full length, virulence-associated sequences. Here, we review the molecular mechanisms by which PB1-F2 may affect influenza virulence, and factors associated with the evolution and selection of this protein.<\/jats:p>","DOI":"10.3390\/ijms19010096","type":"journal-article","created":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T10:58:47Z","timestamp":1514545127000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Evolution and Virulence of Influenza A Virus Protein PB1-F2"],"prefix":"10.3390","volume":"19","author":[{"given":"Ram","family":"Kamal","sequence":"first","affiliation":[{"name":"Battelle Memorial Institute, Atlanta, GA 30329, USA"},{"name":"Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Alymova","sequence":"additional","affiliation":[{"name":"Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"York","sequence":"additional","affiliation":[{"name":"Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.virusres.2014.03.015","article-title":"Molecular mechanisms enhancing the proteome of influenza a viruses: An overview of recently discovered proteins","volume":"185","author":"Vasin","year":"2014","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.virol.2017.05.002","article-title":"PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus by suppressing early immune responses in swine","volume":"508","author":"Xu","year":"2017","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vidy, A., Maisonnasse, P., Da Costa, B., Delmas, B., Chevalier, C., and Le Goffic, R. 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