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Little is known about the role of mutations in the viral neuraminidase (NA) that accompanied bird-to-human transmission to support AIV infection of mammals. Here, after detailed analysis of the NA sequence of human H5N1 viruses, we studied the role of A46D, L204M, S319F and S430G mutations in virus fitness\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Although H5N1 AIV carrying avian- or human-like NAs had similar replication efficiency in avian cells, human-like NA enhanced virus replication in human airway epithelia. The L204M substitution consistently reduced NA activity of H5N1 and nine other influenza viruses carrying NA of groups 1 and 2, indicating a universal effect. Compared to the avian ancestor, human-like H5N1 virus has less NA incorporated in the virion, reduced levels of viral NA RNA replication and NA expression. We also demonstrate increased accumulation of NA at the plasma membrane, reduced virus release and enhanced cell-to-cell spread. Furthermore, NA mutations increased virus binding to human-type receptors. While not affecting high virulence of H5N1 in chickens, the studied NA mutations modulated virulence and replication of H5N1 AIV in mice and to a lesser extent in ferrets. Together, mutations in the NA of human H5N1 viruses play different roles in infection of mammals without affecting virulence or transmission in chickens. These results are important to understand the genetic determinants for replication of AIV in mammals and should assist in the prediction of AIV with zoonotic potential.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011135","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T13:41:23Z","timestamp":1675690883000},"page":"e1011135","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Phenotypic effects of mutations observed in the neuraminidase of human origin H5N1 influenza A viruses"],"prefix":"10.1371","volume":"19","author":[{"given":"David","family":"Scheibner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Salaheldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Bagato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca M.","family":"Zaeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Mostafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Blohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed 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Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003\u20132020. Available online at: https:\/\/www.who.int\/influenza\/human_animal_interface\/2020_10_07_tableH5N1.pdf?ua=1 (last accessed 29-07-2020). 2020."},{"issue":"5","key":"ppat.1011135.ref015","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"},{"issue":"2","key":"ppat.1011135.ref016","doi-asserted-by":"crossref","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"},{"issue":"13","key":"ppat.1011135.ref017","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2807\/1560-7917.ES2015.20.13.21085","article-title":"Emergence of a novel cluster of influenza 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flanking the neuraminidase catalytic site","volume":"98","author":"R Mogling","year":"2017","journal-title":"J Gen Virol"},{"issue":"23","key":"ppat.1011135.ref024","doi-asserted-by":"crossref","first-page":"12531","DOI":"10.1128\/JVI.01889-13","article-title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","volume":"87","author":"KA Hooper","year":"2013","journal-title":"J Virol"},{"issue":"1","key":"ppat.1011135.ref025","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1038\/s41467-021-25713-1","article-title":"Glycan remodeled erythrocytes facilitate antigenic characterization of recent A\/H3N2 influenza viruses","volume":"12","author":"F Broszeit","year":"2021","journal-title":"Nature Communications"},{"issue":"15","key":"ppat.1011135.ref026","doi-asserted-by":"crossref","first-page":"8418","DOI":"10.1128\/JVI.77.15.8418-8425.2003","article-title":"Overexpression of the alpha-2,6-sialyltransferase in MDCK cells increases influenza virus sensitivity to neuraminidase inhibitors","volume":"77","author":"M Matrosovich","year":"2003","journal-title":"J Virol"},{"issue":"16","key":"ppat.1011135.ref027","doi-asserted-by":"crossref","first-page":"8060","DOI":"10.1128\/JVI.00384-06","article-title":"Infection of human airway epithelium by human and avian strains of influenza a virus","volume":"80","author":"CI Thompson","year":"2006","journal-title":"J Virol"},{"issue":"10","key":"ppat.1011135.ref028","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00080-19","article-title":"Tropism and Infectivity of a Seasonal A(H1N1) and a Highly Pathogenic Avian A(H5N1) Influenza Virus in Primary Differentiated Ferret Nasal Epithelial Cell Cultures","volume":"93","author":"H Zeng","year":"2019","journal-title":"J Virol"},{"issue":"23","key":"ppat.1011135.ref029","doi-asserted-by":"crossref","first-page":"11773","DOI":"10.1128\/JVI.75.23.11773-11780.2001","article-title":"Amino acids responsible for the absolute sialidase activity of the influenza A virus neuraminidase: relationship to growth in the duck intestine","volume":"75","author":"D Kobasa","year":"2001","journal-title":"J Virol"},{"issue":"18","key":"ppat.1011135.ref030","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"},{"issue":"8","key":"ppat.1011135.ref031","doi-asserted-by":"crossref","first-page":"e1007233","DOI":"10.1371\/journal.ppat.1007233","article-title":"Kinetic analysis of the influenza A virus HA\/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces","volume":"14","author":"H Guo","year":"2018","journal-title":"PLoS 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inhibited by human mucus but not swine mucus","volume":"89","author":"M Zanin","year":"2015","journal-title":"J Virol"},{"issue":"8","key":"ppat.1011135.ref035","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1128\/JVI.75.8.3766-3770.2001","article-title":"Adaptation of influenza A viruses to cells expressing low levels of sialic acid leads to loss of neuraminidase activity","volume":"75","author":"MT Hughes","year":"2001","journal-title":"J Virol"},{"issue":"2","key":"ppat.1011135.ref036","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00868-16","article-title":"An amino acid in the stalk domain of N1 neuraminidase is critical for enzymatic activity","volume":"91","author":"M Zanin","year":"2017","journal-title":"J Virol"},{"issue":"3","key":"ppat.1011135.ref037","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.chom.2013.02.008","article-title":"Defining influenza A virus hemagglutinin antigenic drift by sequential monoclonal antibody 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Lin","year":"2016","journal-title":"Vet Res"},{"issue":"10","key":"ppat.1011135.ref049","doi-asserted-by":"crossref","first-page":"e1001136","DOI":"10.1371\/journal.ppat.1001136","article-title":"Transforming growth factor-\u03b2: Activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis","volume":"6","author":"CM Carlson","year":"2010","journal-title":"PLOS Pathog"},{"key":"ppat.1011135.ref050","doi-asserted-by":"crossref","first-page":"38388","DOI":"10.1038\/srep38388","article-title":"Risk assessment of recent Egyptian H5N1 influenza viruses","volume":"6","author":"AS Arafa","year":"2016","journal-title":"Sci Rep"},{"issue":"5","key":"ppat.1011135.ref051","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1128\/JVI.02885-12","article-title":"Tropism and infectivity of influenza virus, including highly pathogenic avian H5N1 virus, in ferret tracheal differentiated primary epithelial cell cultures","volume":"87","author":"H Zeng","year":"2013","journal-title":"J Virol"},{"issue":"4","key":"ppat.1011135.ref052","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.2353\/ajpath.2007.070248","article-title":"Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals","volume":"171","author":"D van Riel","year":"2007","journal-title":"Am J Pathol"},{"issue":"22","key":"ppat.1011135.ref053","doi-asserted-by":"crossref","first-page":"11831","DOI":"10.1128\/JVI.01460-10","article-title":"A 27-amino-acid deletion in the neuraminidase stalk supports replication of an avian H2N2 influenza A virus in the respiratory tract of chickens","volume":"84","author":"EM Sorrell","year":"2010","journal-title":"J Virol"},{"issue":"19","key":"ppat.1011135.ref054","doi-asserted-by":"crossref","first-page":"10539","DOI":"10.1128\/JVI.00967-13","article-title":"The short stalk length of highly pathogenic avian influenza H5N1 virus neuraminidase limits transmission of pandemic H1N1 virus in ferrets","volume":"87","author":"D Blumenkrantz","year":"2013","journal-title":"J Virol"},{"issue":"6088","key":"ppat.1011135.ref055","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"},{"issue":"1","key":"ppat.1011135.ref056","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 Pathogens"},{"issue":"3","key":"ppat.1011135.ref057","doi-asserted-by":"crossref","first-page":"e59889","DOI":"10.1371\/journal.pone.0059889","article-title":"Reassortment between Avian H5N1 and Human Influenza Viruses Is Mainly Restricted to the Matrix and Neuraminidase Gene Segments","volume":"8","author":"EJA Schrauwen","year":"2013","journal-title":"PLOS ONE"},{"issue":"1","key":"ppat.1011135.ref058","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12985-017-0697-5","article-title":"Isolation and genetic characterization of a novel 2.2.1.2a H5N1 virus from a vaccinated meat-turkeys flock in Egypt","volume":"14","author":"AH Salaheldin","year":"2017","journal-title":"Virol J"},{"key":"ppat.1011135.ref059","first-page":"183","volume-title":"Human Cell Culture Protocols","author":"ML Fulcher","year":"2005"},{"issue":"1\u20132","key":"ppat.1011135.ref060","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jviromet.2011.08.025","article-title":"A differentiated porcine bronchial epithelial cell culture model for studying human adenovirus tropism and virulence","volume":"178","author":"E Lam","year":"2011","journal-title":"J Virol 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Chapter 2.3.4.\u2014Avian influenza. Available at: http:\/\/www.oie.int\/fileadmin\/Home\/fr\/Health_standards\/tahm\/2.03.04_AI.pdf. 2015."},{"issue":"12","key":"ppat.1011135.ref063","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1099\/jgv.0.000648","article-title":"Progressive glycosylation of the haemagglutinin of avian influenza H5N1 modulates virus replication, virulence and chicken-to-chicken transmission without significant impact on antigenic drift","volume":"97","author":"EM Abdelwhab","year":"2016","journal-title":"J Gen Virol"},{"issue":"6044","key":"ppat.1011135.ref064","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1126\/science.1204839","article-title":"A highly conserved neutralizing epitope on group 2 influenza A viruses","volume":"333","author":"DC Ekiert","year":"2011","journal-title":"Science"},{"key":"ppat.1011135.ref065","doi-asserted-by":"crossref","first-page":"6553","DOI":"10.1038\/ncomms7553","article-title":"Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck","volume":"6","author":"H Zaraket","year":"2015","journal-title":"Nat Commun"},{"key":"ppat.1011135.ref066","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-4939-8678-1_5","article-title":"Purification and Proteomics of Influenza Virions","volume":"1836","author":"EC Hutchinson","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"36","key":"ppat.1011135.ref067","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1016\/j.vaccine.2010.06.075","article-title":"Qualitative and quantitative analyses of virtually all subtypes of influenza A and B viral neuraminidases using antibodies targeting the universally conserved sequences","volume":"28","author":"C Gravel","year":"2010","journal-title":"Vaccine"},{"issue":"4","key":"ppat.1011135.ref068","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3324\/haematol.2021.280154","article-title":"Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines","volume":"107","author":"S Michalik","year":"2022","journal-title":"Haematologica"},{"key":"ppat.1011135.ref069","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0076-6879(90)82008-P","article-title":"Quantitation of protein","volume":"182","author":"CM Stoscheck","year":"1990","journal-title":"Methods Enzymol"},{"issue":"5","key":"ppat.1011135.ref070","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"JR Wisniewski","year":"2009","journal-title":"Nat Methods"},{"key":"ppat.1011135.ref071","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"J Cox","year":"2008","journal-title":"Nature Biotech"},{"issue":"D1","key":"ppat.1011135.ref072","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","author":"C. UniProt","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"7347","key":"ppat.1011135.ref073","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10098","article-title":"Global quantification of mammalian gene expression control","volume":"473","author":"B Schwanhausser","year":"2011","journal-title":"Nature"},{"issue":"3","key":"ppat.1011135.ref074","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1128\/JVI.80.3.1332-1339.2006","article-title":"Composition of pseudorabies virus particles lacking tegument protein US3, UL47, or UL49 or envelope glycoprotein E","volume":"80","author":"K Michael","year":"2006","journal-title":"J Virol"},{"issue":"5","key":"ppat.1011135.ref075","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.4049\/jimmunol.126.5.1814","article-title":"Expression of influenza A virus internal antigens on the surface of infected P815 cells","volume":"126","author":"JW Yewdell","year":"1981","journal-title":"J Immunol"},{"issue":"7","key":"ppat.1011135.ref076","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"ppat.1011135.ref077","doi-asserted-by":"crossref","first-page":"27211","DOI":"10.1038\/srep27211","article-title":"Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses","volume":"6","author":"B Hoffmann","year":"2016","journal-title":"Sci Rep"},{"issue":"12","key":"ppat.1011135.ref078","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1007\/s007050170002","article-title":"Universal primer set for the full-length amplification of all influenza A viruses","volume":"146","author":"E Hoffmann","year":"2001","journal-title":"Arch Virol"},{"issue":"11","key":"ppat.1011135.ref079","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1021\/jm051197e","article-title":"MolDock: a new technique for high-accuracy molecular docking","volume":"49","author":"R Thomsen","year":"2006","journal-title":"J Med Chem"},{"issue":"1","key":"ppat.1011135.ref080","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1038\/s41467-021-26409-2","article-title":"Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus","volume":"12","author":"GA Arunkumar","year":"2021","journal-title":"Nature Communications"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011135","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T13:53:01Z","timestamp":1676555581000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011135"}},"subtitle":[],"editor":[{"given":"Anice C.","family":"Lowen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,2,6]]},"references-count":80,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011135","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,6]]}}}