{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:21:07Z","timestamp":1784251267847,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T00:00:00Z","timestamp":1523404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["12038611\u2010000281"],"award-info":[{"award-number":["12038611\u2010000281"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["DIA.5\/JSPS 1\/2557"],"award-info":[{"award-number":["DIA.5\/JSPS 1\/2557"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003485","name":"Heiwa Nakajima Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003485","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>The rapidly evolvable influenza A virus has caused pandemics linked to millions of deaths in the past century. Influenza A viruses are categorized by H (hemagglutinin; <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) and N (neuraminidase; NA) proteins expressed on the viral envelope surface. Analyses of past pandemics suggest that the <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> gene segment comes from a nonhuman virus, which is then introduced into an immunologically na\u00efve human population with potentially devastating consequences. As a prerequisite for infection, the nonhuman <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> molecules of H1\u2013H16 viruses must be able to bind to specific sialyl receptors on the host cell surface along the human respiratory tract. Thus, additional insight into the structures of host cell glycans and how different <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>s interact with different glycans might provide new insight into the mechanisms underlying sustained infection and transmission in humans. In this work, we identified the sialyl <jats:italic>N<\/jats:italic>\u2010glycans found in normal human alveoli and characterized the influenza viruses that preferentially bound to these different structures. We also determined the amino acid changes in <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> that were linked to a switch of receptor\u2010binding preference from nonhuman to pandemic, as well as pandemic to seasonal. Our data provide insight into why seasonal viruses are associated with reduced alveolar infection and damage and suggest new considerations for designing anti\u2010<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> vaccines and drugs. The results provide a better understanding of viral tropism and pathogenesis in humans that will be important for prediction and surveillance of zoonotic, pandemic, and epidemic influenza outbreaks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Database<\/jats:title><jats:p>The novel hemagglutinin nucleotide sequences reported here were deposited in <jats:styled-content style=\"fixed-case\">GISAID<\/jats:styled-content> under the accession numbers of EPI685738 for A\/Yamaguchi\/20\/2006(H1N1) and EPI685740 for A\/Kitakyushu\/10\/2006(H1N1).<\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.14431","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T14:02:02Z","timestamp":1521122522000},"page":"1611-1634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["<i>N<\/i>\u2010glycan structures of human alveoli provide insight into influenza A virus infection and pathogenesis"],"prefix":"10.1111","volume":"285","author":[{"given":"Nongluk","family":"Sriwilaijaroen","sequence":"first","affiliation":[{"name":"Department of Preclinical Sciences Faculty of Medicine Thammasat University Pathumthani Thailand"},{"name":"College of Life and Health Sciences Chubu University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010ichi","family":"Nakakita","sequence":"additional","affiliation":[{"name":"Department of Functional Glycomics Life Science Research Center Kagawa University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Kondo","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Nagoya City University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Yagi","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Nagoya City University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Nagoya City University Japan"},{"name":"Institute for Molecular Science and Okazaki Institute for Integrative Biosciences National Institutes of Natural Sciences Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeomi","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry Faculty of Agriculture Shizuoka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"College of Engineering Chubu University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kawahara","sequence":"additional","affiliation":[{"name":"College of Engineering Chubu University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Kyoto Prefectural University of Medicine Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Kanai","sequence":"additional","affiliation":[{"name":"The Institute of Scientific and Industrial Research Osaka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Ono","sequence":"additional","affiliation":[{"name":"The Institute of Scientific and Industrial Research Osaka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hirabayashi","sequence":"additional","affiliation":[{"name":"Department of Functional Glycomics Life Science Research Center Kagawa University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"The Institute of Scientific and Industrial Research Osaka University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Chubu University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1292-6_38"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002068"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2206.151752"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2009.131082"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196602032740502"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.025"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1107.041313"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003223"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.19.9300-9305.2000"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1375"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.7367-7373.1998"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.01.015"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016302"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000709"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0909-797"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013768"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1152"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06322-11"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066325"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.12.024"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.11.004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1651"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00068-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.11.002"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.10.006"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10831"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02737-09"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1186430"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412040200"},{"key":"e_1_2_9_31_1","first-page":"95","volume-title":"Influenza Virology: Current Topics","author":"Matrosovich MN","year":"2006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218841110"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.18.9605-9611.2004"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100115"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwm038"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323162111"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.588541"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.01.010"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-11-170"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1610.100508"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.20506\/rst.28.1.1870"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.425819"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(85)90104-5"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-008-9193-x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.03.004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.044974-0"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2015.04.001"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01675-15"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv193"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00053a037"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a122703"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwg032"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.8.4139-4146.2005"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1292-6_10"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.14431","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.14431","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.14431","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.14431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T22:14:20Z","timestamp":1694384060000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.14431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,11]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/febs.14431"],"URL":"https:\/\/doi.org\/10.1111\/febs.14431","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,11]]},"assertion":[{"value":"2017-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}