{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:25:51Z","timestamp":1777098351587,"version":"3.51.4"},"reference-count":94,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS","award":["15K09576"],"award-info":[{"award-number":["15K09576"]}]},{"name":"JSPS","award":["20KK0199"],"award-info":[{"award-number":["20KK0199"]}]},{"name":"JSPS","award":["21K08510"],"award-info":[{"award-number":["21K08510"]}]},{"DOI":"10.13039\/100020236","name":"Japan Foundation for Pediatric Research","doi-asserted-by":"publisher","award":["16-013"],"award-info":[{"award-number":["16-013"]}],"id":[{"id":"10.13039\/100020236","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003837","name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008670","name":"Terumo Foundation for Life Sciences and Arts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008670","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oshimo Foundation"},{"DOI":"10.13039\/501100003485","name":"Heiwa Nakajima Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003485","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008965","name":"Takahashi Industrial and Economic Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008965","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The incidence of human infection by zoonotic avian influenza viruses, especially H5N1 and H7N9 viruses, has increased. Current zoonotic H7N9 avian influenza viruses (identified since 2013) emerged during reassortment of viruses belonging to different subtypes. Despite analyses of their genetic background, we do not know why current H7N9 viruses are zoonotic. Therefore, there is a need to identify the factor(s) responsible for the extended host tropism that enables these viruses to infect humans as well as birds. To identify H7N9-specific amino acids that confer zoonotic properties on H7N9 viruses, we performed multiple alignment of the hemagglutinin (HA) amino acid sequences of A\/Shanghai\/1\/2013 (H7N9) and A\/duck\/Zhejiang\/12\/2011(H7N3) (a putative, non- or less zoonotic HA donor to the zoonotic H7N9 virus). We also analyze the function of an H7N9 HA-specific amino acid with respect to HA acid stability, and evaluated the effect of acid stability on viral infectivity and virulence in a mouse model. HA2-116D, preserved in current zoonotic H7N9 viruses, was crucial for loss of HA acid stability. The acid-labile HA protein in H7 viruses played an important role in infection of human airway epithelial cells; HA2-116D contributed to infection and replication of H7 viruses. Finally, HA2-116D served as a H7 virulence factor in mice. These results suggest that acid-labile HA harboring HA2-116D confers zoonotic characteristics on H7N9 virus and that future novel zoonotic avian viruses could emerge from non-zoonotic H7 viruses via acquisition of mutations that remove HA acid stability.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012427","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T17:37:33Z","timestamp":1729618653000},"page":"e1012427","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["The host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6881-0817","authenticated-orcid":true,"given":"Tomo","family":"Daidoji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Sadakane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Garan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihito","family":"Kawashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuha","family":"Arai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"issue":"9918","key":"ppat.1012427.ref001","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0140-6736(14)60111-2","article-title":"Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study","volume":"383","author":"H Chen","year":"2014","journal-title":"Lancet"},{"issue":"5","key":"ppat.1012427.ref002","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1073\/pnas.0308352100","article-title":"Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome.","volume":"101","author":"RA Fouchier","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3\u20134","key":"ppat.1012427.ref003","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.vetmic.2009.08.022","article-title":"(Highly pathogenic) avian influenza as a zoonotic agent.","volume":"140","author":"D Kalthoff","year":"2010","journal-title":"Vet Microbiol"},{"issue":"17","key":"ppat.1012427.ref004","doi-asserted-by":"crossref","first-page":"9654","DOI":"10.1073\/pnas.160270697","article-title":"Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates","volume":"97","author":"YP Lin","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"issue":"17","key":"ppat.1012427.ref005","doi-asserted-by":"crossref","first-page":"8671","DOI":"10.1128\/JVI.01034-15","article-title":"Epidemiology, Evolution, and Recent Outbreaks of Avian Influenza Virus in China","volume":"89","author":"S Su","year":"2015","journal-title":"J Virol"},{"issue":"5","key":"ppat.1012427.ref006","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1056\/NEJMc1502983","article-title":"Human Infection with a Novel Avian Influenza A(H5N6) Virus.","volume":"373","author":"ZF Yang","year":"2015","journal-title":"N Engl J Med"},{"issue":"9887","key":"ppat.1012427.ref007","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S0140-6736(13)61207-6","article-title":"Human infection with avian influenza A H7N9 virus: an assessment of clinical severity","volume":"382","author":"H Yu","year":"2013","journal-title":"Lancet"},{"issue":"5","key":"ppat.1012427.ref008","doi-asserted-by":"crossref","first-page":"814","DOI":"10.3201\/eid1805.111852","article-title":"Influenza virus A (H10N7) in chickens and poultry abattoir workers, Australia.","volume":"18","author":"GG Arzey","year":"2012","journal-title":"Emerg Infect Dis"},{"issue":"9182","key":"ppat.1012427.ref009","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/S0140-6736(99)03311-5","article-title":"Human infection with influenza H9N2","volume":"354","author":"M Peiris","year":"1999","journal-title":"Lancet"},{"issue":"12","key":"ppat.1012427.ref010","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.3201\/eid1012.040961","article-title":"Human illness from avian influenza H7N3, British Columbia","volume":"10","author":"SA Tweed","year":"2004","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"ppat.1012427.ref011","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.3201\/eid1909.130087","article-title":"Highly pathogenic avian influenza A(H7N3) virus in poultry workers, Mexico, 2012.","volume":"19","author":"I Lopez-Martinez","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"7","key":"ppat.1012427.ref012","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.3201\/eid1807.111913","article-title":"Low pathogenic avian influenza A (H7N2) virus infection in immunocompromised adult, New York, USA, 2003.","volume":"18","author":"B Ostrowsky","year":"2012","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"ppat.1012427.ref013","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/cit479","article-title":"Origin and molecular characteristics of a novel 2013 avian influenza A(H6N1) virus causing human infection in Taiwan.","volume":"57","author":"J Yuan","year":"2013","journal-title":"Clin Infect Dis"},{"issue":"3","key":"ppat.1012427.ref014","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jinf.2018.07.005","article-title":"Human infection with an avian-origin influenza A (H7N4) virus in Jiangsu: A potential threat to China.","volume":"77","author":"P Gao","year":"2018","journal-title":"J Infect"},{"issue":"9409","key":"ppat.1012427.ref015","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0140-6736(04)15589-X","article-title":"Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands","volume":"363","author":"M Koopmans","year":"2004","journal-title":"Lancet"},{"issue":"3","key":"ppat.1012427.ref016","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jinf.2018.06.002","article-title":"First human infection by a novel avian influenza A(H7N4) virus.","volume":"77","author":"XC Tong","year":"2018","journal-title":"J Infect"},{"issue":"10","key":"ppat.1012427.ref017","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.21037\/qims-21-592","article-title":"A human infection case with avian-origin H10N3 influenza virus.","volume":"11","author":"J Jing","year":"2021","journal-title":"Quant Imaging Med Surg"},{"issue":"11","key":"ppat.1012427.ref018","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1056\/NEJMc2112416","article-title":"Human Infection with an Avian-Origin Influenza A (H10N3) Virus.","volume":"386","author":"X Qi","year":"2022","journal-title":"N Engl J Med"},{"issue":"4","key":"ppat.1012427.ref019","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s13337-022-00800-z","article-title":"Avian influenza revisited: concerns and constraints.","volume":"33","author":"R Kanaujia","year":"2022","journal-title":"Virusdisease."},{"issue":"9881","key":"ppat.1012427.ref020","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1016\/S0140-6736(13)60903-4","article-title":"Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome","volume":"381","author":"Y Chen","year":"2013","journal-title":"Lancet"},{"issue":"20","key":"ppat.1012427.ref021","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1304459","article-title":"Human infection with a novel avian-origin influenza A (H7N9) virus.","volume":"368","author":"R Gao","year":"2013","journal-title":"N Engl J Med"},{"issue":"6","key":"ppat.1012427.ref022","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/tbed.12327","article-title":"A Systematic Review of the Comparative Epidemiology of Avian and Human Influenza A H5N1 and H7N9\u2014Lessons and Unanswered Questions.","volume":"63","author":"C Bui","year":"2016","journal-title":"Transbound Emerg Dis."},{"issue":"2","key":"ppat.1012427.ref023","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jmii.2015.06.004","article-title":"Epidemiology of human influenza A(H7N9) infection in Hong Kong.","volume":"50","author":"YH Leung","year":"2017","journal-title":"J Microbiol Immunol Infect"},{"issue":"4","key":"ppat.1012427.ref024","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00445-13","article-title":"H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity.","volume":"4","author":"DM Morens","year":"2013","journal-title":"mBio"},{"issue":"16","key":"ppat.1012427.ref025","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1017\/S0950268815001570","article-title":"The pandemic potential of avian influenza A(H7N9) virus: a review.","volume":"143","author":"WD Tanner","year":"2015","journal-title":"Epidemiol Infect"},{"issue":"15","key":"ppat.1012427.ref026","doi-asserted-by":"crossref","first-page":"20453","DOI":"10.2807\/ese.18.15.20453-en","article-title":"Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013.","volume":"18","author":"T Kageyama","year":"2013","journal-title":"Euro Surveill"},{"issue":"9881","key":"ppat.1012427.ref027","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1016\/S0140-6736(13)60938-1","article-title":"Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses","volume":"381","author":"D Liu","year":"2013","journal-title":"Lancet"},{"key":"ppat.1012427.ref028","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/srep02318","article-title":"Towards a better understanding of the novel avian-origin H7N9 influenza A virus in China.","volume":"3","author":"Y Wang","year":"2013","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1012427.ref029","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0092-8674(85)90157-6","article-title":"Fusion mutants of the influenza virus hemagglutinin glycoprotein","volume":"40","author":"RS Daniels","year":"1985","journal-title":"Cell"},{"key":"ppat.1012427.ref030","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.bi.56.070187.002053","article-title":"The structure and function of the hemagglutinin membrane glycoprotein of influenza virus","volume":"56","author":"DC Wiley","year":"1987","journal-title":"Annu Rev Biochem"},{"issue":"6492","key":"ppat.1012427.ref031","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/371037a0","article-title":"Structure of influenza haemagglutinin at the pH of membrane fusion","volume":"371","author":"PA Bullough","year":"1994","journal-title":"Nature"},{"issue":"6","key":"ppat.1012427.ref032","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1023\/A:1010467106305","article-title":"Virus membrane fusion proteins: biological machines that undergo a metamorphosis","volume":"20","author":"RE Dutch","year":"2000","journal-title":"Biosci Rep"},{"key":"ppat.1012427.ref033","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.biochem.69.1.531","article-title":"Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin","volume":"69","author":"JJ Skehel","year":"2000","journal-title":"Annu Rev Biochem"},{"issue":"6","key":"ppat.1012427.ref034","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1080\/09687860400017784","article-title":"Class I and class II viral fusion protein structures reveal similar principles in membrane fusion","volume":"21","author":"DJ Schibli","year":"2004","journal-title":"Mol Membr Biol"},{"issue":"1","key":"ppat.1012427.ref035","doi-asserted-by":"crossref","DOI":"10.3390\/v12010082","article-title":"Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes.","volume":"12","author":"T Daidoji","year":"2020","journal-title":"Viruses"},{"issue":"17","key":"ppat.1012427.ref036","doi-asserted-by":"crossref","first-page":"10627","DOI":"10.1074\/jbc.M114.611327","article-title":"Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH","volume":"290","author":"T Daidoji","year":"2015","journal-title":"J Biol Chem"},{"issue":"2","key":"ppat.1012427.ref037","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":"8","key":"ppat.1012427.ref038","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1128\/JVI.02238-08","article-title":"Amino acid residues in the fusion peptide pocket regulate the pH of activation of the H5N1 influenza virus hemagglutinin protein","volume":"83","author":"ML Reed","year":"2009","journal-title":"J Virol"},{"issue":"9","key":"ppat.1012427.ref039","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1128\/JVI.03110-12","article-title":"The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice","volume":"87","author":"H Zaraket","year":"2013","journal-title":"J Virol"},{"issue":"1","key":"ppat.1012427.ref040","article-title":"Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models","volume":"93","author":"X Sun","year":"2018","journal-title":"J Virol"},{"issue":"8","key":"ppat.1012427.ref041","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1128\/JVI.00057-15","article-title":"Influenza hemagglutinin (HA) stem region mutations that stabilize or destabilize the structure of multiple HA subtypes.","volume":"89","author":"L Byrd-Leotis","year":"2015","journal-title":"J Virol"},{"issue":"10","key":"ppat.1012427.ref042","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.micinf.2004.05.002","article-title":"Endocytosis of influenza viruses.","volume":"6","author":"M Lakadamyali","year":"2004","journal-title":"Microbes Infect \/ Institut Pasteur"},{"issue":"4","key":"ppat.1012427.ref043","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/S0955-0674(03)00081-4","article-title":"Insider information: what viruses tell us about endocytosis","volume":"15","author":"L Pelkmans","year":"2003","journal-title":"Curr Opin Cell Biol"},{"issue":"2","key":"ppat.1012427.ref044","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1128\/jvi.51.2.497-504.1984","article-title":"Uncoating of influenza virus in endosomes","volume":"51","author":"A Yoshimura","year":"1984","journal-title":"J Virol"},{"issue":"2","key":"ppat.1012427.ref045","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/bies.201400133","article-title":"One-way trip: influenza virus\u2019 adaptation to gallinaceous poultry may limit its pandemic potential","volume":"37","author":"JS Long","year":"2015","journal-title":"Bioessays"},{"issue":"17","key":"ppat.1012427.ref046","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00058-19","article-title":"Influenza Virus with Increased pH of Hemagglutinin Activation Has Improved Replication in Cell Culture but at the Cost of Infectivity in Human Airway Epithelium","volume":"93","author":"A Singanayagam","year":"2019","journal-title":"J Virol"},{"issue":"23","key":"ppat.1012427.ref047","doi-asserted-by":"crossref","first-page":"11599","DOI":"10.1128\/JVI.01393-08","article-title":"Experimental evolution of human influenza virus H3 hemagglutinin in the mouse lung identifies adaptive regions in HA1 and HA2","volume":"82","author":"L Keleta","year":"2008","journal-title":"J Virol"},{"issue":"Pt 5","key":"ppat.1012427.ref048","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1099\/vir.0.035782-0","article-title":"Altered receptor specificity and fusion activity of the haemagglutinin contribute to high virulence of a mouse-adapted influenza A virus","volume":"93","author":"I Koerner","year":"2012","journal-title":"J Gen Virol"},{"issue":"2","key":"ppat.1012427.ref049","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/viro.1997.8626","article-title":"Adaptation of egg-grown and transfectant influenza viruses for growth in mammalian cells: selection of hemagglutinin mutants with elevated pH of membrane fusion","volume":"233","author":"YP Lin","year":"1997","journal-title":"Virology"},{"key":"ppat.1012427.ref050","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"},{"issue":"7468","key":"ppat.1012427.ref051","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/nature12476","article-title":"Limited airborne transmission of H7N9 influenza A virus between ferrets","volume":"501","author":"M Richard","year":"2013","journal-title":"Nature"},{"issue":"3","key":"ppat.1012427.ref052","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1128\/JVI.02959-13","article-title":"Novel H7N9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the guinea pig model","volume":"88","author":"JD Gabbard","year":"2014","journal-title":"J Virol"},{"issue":"9","key":"ppat.1012427.ref053","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.1128\/JVI.00134-16","article-title":"Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013\u20132015","volume":"90","author":"JA Belser","year":"2016","journal-title":"J Virol"},{"issue":"17","key":"ppat.1012427.ref054","doi-asserted-by":"crossref","first-page":"9911","DOI":"10.1128\/JVI.01175-13","article-title":"Increased acid stability of the hemagglutinin protein enhances H5N1 influenza virus growth in the upper respiratory tract but is insufficient for transmission in ferrets","volume":"87","author":"H Zaraket","year":"2013","journal-title":"J Virol"},{"issue":"1","key":"ppat.1012427.ref055","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/(SICI)1097-4652(199807)176:1<216::AID-JCP23>3.0.CO;2-3","article-title":"Primary cell cultures from murine kidney and heart differ in endosomal pH","volume":"176","author":"SL Rybak","year":"1998","journal-title":"J Cell Physiol"},{"issue":"3","key":"ppat.1012427.ref056","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/0092-8674(82)90219-7","article-title":"Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin","volume":"28","author":"B Tycko","year":"1982","journal-title":"Cell"},{"issue":"6","key":"ppat.1012427.ref057","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1083\/jcb.97.6.1762","article-title":"Rapid acidification of endocytic vesicles containing asialoglycoprotein in cells of a human hepatoma line","volume":"97","author":"B Tycko","year":"1983","journal-title":"J Cell Biol"},{"issue":"3","key":"ppat.1012427.ref058","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/0092-8674(84)90414-8","article-title":"Segregation of transferrin to a mildly acidic (pH 6.5) para-Golgi compartment in the recycling pathway.","volume":"37","author":"DJ Yamashiro","year":"1984","journal-title":"Cell"},{"issue":"6 Pt 1","key":"ppat.1012427.ref059","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1083\/jcb.105.6.2723","article-title":"Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells","volume":"105","author":"DJ Yamashiro","year":"1987","journal-title":"J Cell Biol"},{"issue":"20","key":"ppat.1012427.ref060","doi-asserted-by":"crossref","first-page":"6186","DOI":"10.1073\/pnas.79.20.6186","article-title":"Receptor-mediated endocytosis of transferrin and the uptake of fe in K562 cells: identification of a nonlysosomal acidic compartment","volume":"79","author":"J van Renswoude","year":"1982","journal-title":"Proc Natl Acad Sci USA"},{"issue":"20","key":"ppat.1012427.ref061","doi-asserted-by":"crossref","first-page":"7119","DOI":"10.1073\/pnas.84.20.7119","article-title":"High-resolution kinetics of transferrin acidification in BALB\/c 3T3 cells: exposure to pH 6 followed by temperature-sensitive alkalinization during recycling","volume":"84","author":"DM Sipe","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"ppat.1012427.ref062","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1016\/S0021-9258(19)67819-1","article-title":"Absence of Na+,K(+)-ATPase regulation of endosomal acidification in K562 erythroleukemia cells. Analysis via inhibition of transferrin recycling by low temperatures","volume":"266","author":"DM Sipe","year":"1991","journal-title":"J Biol Chem"},{"issue":"Pt 1","key":"ppat.1012427.ref063","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1242\/jcs.103.1.211","article-title":"Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome","volume":"103","author":"I Killisch","year":"1992","journal-title":"J Cell Sci"},{"issue":"1","key":"ppat.1012427.ref064","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1083\/jcb.119.1.99","article-title":"Second messengers regulate endosomal acidification in Swiss 3T3 fibroblasts","volume":"119","author":"K Zen","year":"1992","journal-title":"J Cell Biol"},{"issue":"3","key":"ppat.1012427.ref065","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1128\/JVI.06009-11","article-title":"Enhanced growth of influenza vaccine seed viruses in vero cells mediated by broadening the optimal pH range for virus membrane fusion","volume":"86","author":"S Murakami","year":"2012","journal-title":"J Virol"},{"issue":"2","key":"ppat.1012427.ref066","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/JVI.02005-07","article-title":"The influenza virus resource at the National Center for Biotechnology Information","volume":"82","author":"Y Bao","year":"2008","journal-title":"J Virol"},{"key":"ppat.1012427.ref067","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1136\/vr.160.22.746","article-title":"Low pathogenic H7N2 avian influenza virus confirmed in Wales","volume":"160","author":"Anonymous","year":"2007","journal-title":"Vet Rec"},{"key":"ppat.1012427.ref068","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1471-2334-10-141","article-title":"Assessing the role of contact tracing in a suspected H7N2 influenza A outbreak in humans in Wales.","volume":"10","author":"KT Eames","year":"2010","journal-title":"BMC Infect Dis"},{"issue":"17","key":"ppat.1012427.ref069","doi-asserted-by":"crossref","first-page":"9601","DOI":"10.1128\/JVI.00666-07","article-title":"Differential polymerase activity in avian and mammalian cells determines host range of influenza virus","volume":"81","author":"G Gabriel","year":"2007","journal-title":"J Virol"},{"issue":"10","key":"ppat.1012427.ref070","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."},{"issue":"2","key":"ppat.1012427.ref071","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.virol.2006.12.027","article-title":"Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells","volume":"362","author":"K Labadie","year":"2007","journal-title":"Virology"},{"issue":"18","key":"ppat.1012427.ref072","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"},{"issue":"4","key":"ppat.1012427.ref073","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1128\/JVI.01879-08","article-title":"PB2 protein of a highly pathogenic avian influenza virus strain A\/chicken\/Yamaguchi\/7\/2004 (H5N1) determines its replication potential in pigs.","volume":"83","author":"R Manzoor","year":"2009","journal-title":"J Virol"},{"issue":"11","key":"ppat.1012427.ref074","doi-asserted-by":"crossref","first-page":"5398","DOI":"10.1128\/JVI.75.11.5398-5404.2001","article-title":"Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses","volume":"75","author":"P Massin","year":"2001","journal-title":"J Virol"},{"issue":"24","key":"ppat.1012427.ref075","doi-asserted-by":"crossref","first-page":"13015","DOI":"10.1128\/JVI.01714-09","article-title":"Ostrich involvement in the selection of H5N1 influenza virus possessing mammalian-type amino acids in the PB2 protein","volume":"83","author":"K Shinya","year":"2009","journal-title":"J Virol"},{"issue":"1","key":"ppat.1012427.ref076","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."},{"issue":"7403","key":"ppat.1012427.ref077","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nature10831","article-title":"Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA\/H1N1 virus in ferrets","volume":"486","author":"M Imai","year":"2012","journal-title":"Nature"},{"issue":"6088","key":"ppat.1012427.ref078","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":"3","key":"ppat.1012427.ref079","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00232-006-0861-0","article-title":"Mechanisms of acid and base secretion by the airway epithelium","volume":"211","author":"H Fischer","year":"2006","journal-title":"J Membr Biol"},{"issue":"2","key":"ppat.1012427.ref080","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0378-5173(99)00442-1","article-title":"Determination of baseline human nasal pH and the effect of intranasally administered buffers","volume":"198","author":"N Washington","year":"2000","journal-title":"Int J Pharm"},{"issue":"10","key":"ppat.1012427.ref081","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.tim.2018.03.005","article-title":"Influenza Hemagglutinin Protein Stability, Activation, and Pandemic Risk","volume":"26","author":"CJ Russell","year":"2018","journal-title":"Trends Microbiol"},{"issue":"12","key":"ppat.1012427.ref082","doi-asserted-by":"crossref","first-page":"e1002398","DOI":"10.1371\/journal.ppat.1002398","article-title":"Acid stability of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity.","volume":"7","author":"RM DuBois","year":"2011","journal-title":"PLoS Pathog."},{"issue":"2","key":"ppat.1012427.ref083","doi-asserted-by":"crossref","first-page":"e1003151","DOI":"10.1371\/journal.ppat.1003151","article-title":"Influenza HA subtypes demonstrate divergent phenotypes for cleavage activation and pH of fusion: implications for host range and adaptation.","volume":"9","author":"SE Galloway","year":"2013","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1012427.ref084","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1128\/JVI.02069-09","article-title":"The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity and transmissibility in ducks","volume":"84","author":"ML Reed","year":"2010","journal-title":"J Virol"},{"issue":"7468","key":"ppat.1012427.ref085","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature12392","article-title":"Characterization of H7N9 influenza A viruses isolated from humans","volume":"501","author":"T Watanabe","year":"2013","journal-title":"Nature"},{"issue":"6142","key":"ppat.1012427.ref086","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1126\/science.1239844","article-title":"Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs","volume":"341","author":"H Zhu","year":"2013","journal-title":"Science"},{"issue":"4","key":"ppat.1012427.ref087","doi-asserted-by":"crossref","first-page":"e1005583","DOI":"10.1371\/journal.ppat.1005583","article-title":"Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses.","volume":"12","author":"Y Arai","year":"2016","journal-title":"PLoS Pathog"},{"issue":"14","key":"ppat.1012427.ref088","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"},{"issue":"1\u20132","key":"ppat.1012427.ref089","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0166-0934(01)00437-2","article-title":"Rapid methods for identification of poliovirus isolates and determination of polio neutralizing antibody titers in human sera","volume":"101","author":"A Di Lonardo","year":"2002","journal-title":"J Virol Methods"},{"issue":"11","key":"ppat.1012427.ref090","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"},{"issue":"5","key":"ppat.1012427.ref091","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1073\/pnas.031575198","article-title":"Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes.","volume":"98","author":"CF Basler","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"issue":"21","key":"ppat.1012427.ref092","doi-asserted-by":"crossref","first-page":"13849","DOI":"10.1073\/pnas.212519699","article-title":"Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus.","volume":"99","author":"TM Tumpey","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"ppat.1012427.ref093","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1128\/jvi.67.7.4070-4077.1993","article-title":"Mutational analysis of the vesicular stomatitis virus glycoprotein G for membrane fusion domains","volume":"67","author":"Y Li","year":"1993","journal-title":"J Virol"},{"issue":"4","key":"ppat.1012427.ref094","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/bib\/bbn017","article-title":"MEGA: a biologist-centric software for evolutionary analysis of DNA and protein sequences","volume":"9","author":"S Kumar","year":"2008","journal-title":"Brief Bioinform"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T17:37:59Z","timestamp":1729618679000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012427"}},"subtitle":[],"editor":[{"given":"Kanta","family":"Subbarao","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":94,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012427","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]}}}