{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:52:05Z","timestamp":1790776325366,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2016,4,20]],"date-time":"2016-04-20T00:00:00Z","timestamp":1461110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1005583","type":"journal-article","created":{"date-parts":[[2016,4,20]],"date-time":"2016-04-20T17:34:59Z","timestamp":1461173699000},"page":"e1005583","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":53,"title":["Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses"],"prefix":"10.1371","volume":"12","author":[{"given":"Yasuha","family":"Arai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihito","family":"Kawashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomo","family":"Daidoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madiha S.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad M.","family":"El-Gendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Ikuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Shioda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,4,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1099\/vir.0.062836-0","article-title":"Viral determinants of influenza A virus host range","volume":"95","author":"AV Cauldwell","year":"2014","journal-title":"J Gen Virol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrmicro3367","article-title":"At the centre: influenza A virus ribonucleoproteins","volume":"13","author":"AJ Eisfeld","year":"2015","journal-title":"Nat Rev Microbiol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.virusres.2013.07.017","article-title":"Transmission of influenza A\/H5N1 viruses in mammals","volume":"178","author":"M Imai","year":"2013","journal-title":"Virus Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tim.2011.10.003","article-title":"The changing nature of avian influenza A virus (H5N1)","volume":"20","author":"Y Watanabe","year":"2012","journal-title":"Trends Microbiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"8502","DOI":"10.1128\/JVI.74.18.8502-8512.2000","article-title":"Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals","volume":"74","author":"M Matrosovich","year":"2000","journal-title":"J Virol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1146\/annurev.micro.62.081307.162746","article-title":"Host restriction of avian influenza viruses at the level of the ribonucleoproteins","volume":"62","author":"N Naffakh","year":"2008","journal-title":"Annu Rev Microbiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1126\/science.1062882","article-title":"Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses","volume":"293","author":"M Hatta","year":"2001","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1128\/JVI.67.4.1761-1764.1993","article-title":"A single amino acid in the PB2 gene of influenza A virus is a determinant of host range","volume":"67","author":"EK Subbarao","year":"1993","journal-title":"J Virol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1128\/JVI.01783-09","article-title":"Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host","volume":"84","author":"E de Wit","year":"2010","journal-title":"J Virol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1038\/ncomms6509","article-title":"The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication","volume":"5","author":"W Song","year":"2014","journal-title":"Nat Commun"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"20836","DOI":"10.2807\/1560-7917.ES2014.19.25.20836","article-title":"Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013","volume":"19","author":"D Wang","year":"2014","journal-title":"Euro Surveill"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1371\/journal.ppat.0030133","article-title":"Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice","volume":"3","author":"M Hatta","year":"2007","journal-title":"PLoS Pathog"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1038\/ncomms6021","article-title":"Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts","volume":"5","author":"S Fan","year":"2014","journal-title":"Nat Commun"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"18590","DOI":"10.1073\/pnas.0507415102","article-title":"The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host","volume":"102","author":"G Gabriel","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"12058","DOI":"10.1128\/JVI.79.18.12058-12064.2005","article-title":"Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model","volume":"79","author":"Z Li","year":"2005","journal-title":"J Virol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"21312","DOI":"10.1073\/pnas.0911915106","article-title":"Adaptive strategies of the influenza virus polymerase for replication in humans","volume":"106","author":"A Mehle","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"7491","DOI":"10.1038\/ncomms8491","article-title":"Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus","volume":"6","author":"AS Taft","year":"2015","journal-title":"Nat Commun"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e1001034","DOI":"10.1371\/journal.ppat.1001034","article-title":"Biological and structural characterization of a host-adapting amino acid in influenza virus","volume":"6","author":"S Yamada","year":"2010","journal-title":"PLoS Pathog"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e1002932","DOI":"10.1371\/journal.ppat.1002932","article-title":"Egyptian H5N1 influenza viruses-cause for concern?","volume":"8","author":"G Neumann","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/embor.2012.212","article-title":"Evolution and control of H5N1. A better understanding of the evolution and diversity of H5N1 flu virus and its host species in endemic areas could inform more efficient vaccination and control strategies","volume":"14","author":"Y Watanabe","year":"2013","journal-title":"EMBO Rep"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3201\/eid1901.121080","article-title":"Microevolution of highly pathogenic avian influenza A(H5N1) viruses isolated from humans, Egypt, 2007\u20132011","volume":"19","author":"M Younan","year":"2013","journal-title":"Emerg Infect Dis"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1099\/vir.0.063495-0","article-title":"Molecular characterization of avian influenza H5N1 virus in Egypt and the emergence of a novel endemic subclade","volume":"95","author":"R El-Shesheny","year":"2014","journal-title":"J Gen Virol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e1000252","DOI":"10.1371\/journal.ppat.1000252","article-title":"Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E\/701N","volume":"5","author":"J Steel","year":"2009","journal-title":"PLoS Pathog"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"4687","DOI":"10.1073\/pnas.0912807107","article-title":"Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence","volume":"107","author":"C Li","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1128\/JVI.01633-12","article-title":"Investigation of influenza virus polymerase activity in pig cells","volume":"87","author":"O Moncorge","year":"2013","journal-title":"J Virol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"9978","DOI":"10.1128\/JVI.01134-10","article-title":"Evidence for avian and human host cell factors that affect the activity of influenza virus polymerase","volume":"84","author":"O Moncorge","year":"2010","journal-title":"J Virol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.chom.2015.01.005","article-title":"Influenza virus adaptation PB2-627K modulates nucleocapsid inhibition by the pathogen sensor RIG-I","volume":"17","author":"M Weber","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"e1002068","DOI":"10.1128\/mBio.00081-15","article-title":"Characterization of H5N1 influenza virus variants with hemagglutinin mutations isolated from patients","volume":"6","author":"Y Watanabe","year":"2015","journal-title":"MBio"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1099\/vir.0.032623-0","article-title":"Genetic diversification of H5N1 highly pathogenic avian influenza A virus during replication in wild ducks","volume":"92","author":"Y Watanabe","year":"2011","journal-title":"J Gen Virol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e1002068","DOI":"10.1371\/journal.ppat.1002068","article-title":"Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt","volume":"7","author":"Y Watanabe","year":"2011","journal-title":"PLoS Pathog"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature14008","article-title":"Structure of influenza A polymerase bound to the viral RNA promoter","volume":"516","author":"A Pflug","year":"2014","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nsmb.1421","article-title":"The structural basis for cap binding by influenza virus polymerase subunit PB2","volume":"15","author":"D Guilligay","year":"2008","journal-title":"Nat Struct Mol Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/nature07120","article-title":"Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus","volume":"454","author":"X He","year":"2008","journal-title":"Nature"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nature14009","article-title":"Structural insight into cap-snatching and RNA synthesis by influenza polymerase","volume":"516","author":"S Reich","year":"2014","journal-title":"Nature"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e1000136","DOI":"10.1371\/journal.ppat.1000136","article-title":"Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit","volume":"4","author":"F Tarendeau","year":"2008","journal-title":"PLoS Pathog"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1126\/science.1213362","article-title":"Airborne transmission of influenza A\/H5N1 virus between ferrets","volume":"336","author":"S Herfst","year":"2012","journal-title":"Science"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cell.2014.02.040","article-title":"Identification, characterization, and natural selection of mutations driving airborne transmission of A\/H5N1 virus","volume":"157","author":"M Linster","year":"2014","journal-title":"Cell"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/ncomms1804","article-title":"Adaptive mutations in NEP compensate for defective H5N1 RNA replication in cultured human cells","volume":"3","author":"B Manz","year":"2012","journal-title":"Nat Commun"},{"key":"ref39","first-page":"398","article-title":"The N-terminal region of influenza virus polymerase PB1 adjacent to the PA binding site is involved in replication but not transcription of the viral genome","volume":"4","author":"NT Binh","year":"2013","journal-title":"Front Microbiol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nature04230","article-title":"Characterization of the 1918 influenza virus polymerase genes","volume":"437","author":"JK Taubenberger","year":"2005","journal-title":"Nature"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4149\/av_2013_02_113","article-title":"The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication","volume":"57","author":"E Fodor","year":"2013","journal-title":"Acta Virol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"11911","DOI":"10.1128\/JVI.01565-06","article-title":"Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex","volume":"80","author":"T Deng","year":"2006","journal-title":"J Virol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1371\/journal.ppat.0040011","article-title":"Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus","volume":"4","author":"G Gabriel","year":"2008","journal-title":"PLoS Pathog"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/ncomms1158","article-title":"Differential use of importin-\u03b1 isoforms governs cell tropism and host adaptation of influenza virus","volume":"2","author":"G Gabriel","year":"2011","journal-title":"Nat Commun"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e1002488","DOI":"10.1371\/journal.ppat.1002488","article-title":"Human-like PB2 627K influenza virus polymerase activity is regulated by importin-\u03b11 and -\u03b17","volume":"8","author":"B Hudjetz","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1099\/vir.0.020750-0","article-title":"Evolution of highly pathogenic avian H5N1 influenza viruses and the emergence of dominant variants","volume":"91","author":"G Neumann","year":"2010","journal-title":"J Gen Virol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1126\/science.1121586","article-title":"Large-scale sequence analysis of avian influenza isolates","volume":"311","author":"JC Obenauer","year":"2006","journal-title":"Science"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/nar\/gkf436","article-title":"MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform","volume":"30","author":"K Katoh","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"9679","DOI":"10.1128\/JVI.73.11.9679-9682.1999","article-title":"Rescue of influenza A virus from recombinant DNA","volume":"73","author":"E Fodor","year":"1999","journal-title":"J Virol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1093\/molbev\/msm092","article-title":"MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0","volume":"24","author":"K Tamura","year":"2007","journal-title":"Mol Biol Evol"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1005583","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T22:39:30Z","timestamp":1600468770000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1005583"}},"subtitle":[],"editor":[{"given":"Kanta","family":"Subbarao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,4,20]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1005583","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,20]]}}}