{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:24:12Z","timestamp":1789453452689,"version":"build-2803163510"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"13","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2020,6,16]]},"abstract":"<jats:p>H5 viruses continue to be a threat for public health. Because these viruses are immunologically novel to humans, they could spark a pandemic when adapted to transmit between humans. Avian influenza viruses need several adaptive mutations to bind to human-type receptors, increase hemagglutinin (HA) stability, and replicate in human cells. However, knowledge on adaptive mutations during human infections is limited. A previous study showed substantial diversity within the receptor binding site of H5N1 during human infection. We therefore analyzed the observed amino acid changes phenotypically in a diverse set of assays, including virus replication, stability, and receptor specificity. None of the tested substitutions resulted in a clear step toward a human-adapted virus capable of aerosol transmission. It is notable that acquiring human-type receptor specificity needs multiple amino acid mutations, and that variability at key position 226 is not tolerated, reducing the risk of them being acquired naturally.<\/jats:p>","DOI":"10.1128\/jvi.00195-20","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T09:40:26Z","timestamp":1587462026000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Phenotypic Effects of Substitutions within the Receptor Binding Site of Highly Pathogenic Avian Influenza H5N1 Virus Observed during Human Infection"],"prefix":"10.1128","volume":"94","author":[{"given":"Dirk","family":"Eggink","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Spronken","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roosmarijn","family":"van der Woude","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocynthe","family":"Buzink","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands"},{"name":"Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Broszeit","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"McBride","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA"},{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana A.","family":"Pawestri","sequence":"additional","affiliation":[{"name":"National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivi","family":"Setiawaty","sequence":"additional","affiliation":[{"name":"National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Paulson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA"},{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert-Jan","family":"Boons","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands"},{"name":"Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands"},{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA"},{"name":"Department of Chemistry, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A. M.","family":"Fouchier","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A.","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno D.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060930"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044021"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60493-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.072"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/embj.201387442"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2013.07.017"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.11.5398-5404.2001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000709"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2019.1575700"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005583"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00130-16"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1125548"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(83)90507-x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2013.02.015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.18.8502-8512.2000"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(83)90150-2"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01292-15"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02016-17"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006390"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.054"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218841110"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.11.004"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.10.006"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1213362"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10831"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.03.003"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2013.10.004"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222526"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07000-6"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007836"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02737-09"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.08.035"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2018.03.018"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24257"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2407.171441"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.04.016"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.11.002"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124513"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00081-15"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02004-17"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05264"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135165"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.027"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.12.014"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.048"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12144"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.040"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2017.1338243"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.05.011"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008191"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(93)90056-s"},{"key":"e_1_3_2_53_2","first-page":"35","article-title":"Sialyloligosaccharides of the respiratory epithelium in the selection of human influenza virus receptor specificity","volume":"40","author":"Baum LG","year":"1990","unstructured":"Baum LG, Paulson JC. 1990. Sialyloligosaccharides of the respiratory epithelium in the selection of human influenza virus receptor specificity. Acta Histochem Suppl 40:35\u201338.","journal-title":"Acta Histochem Suppl"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.15.9926-9932.2005"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2004.02.028"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-3-63"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133888"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1236787"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00195-20","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00195-20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:01:04Z","timestamp":1646474464000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00195-20"}},"subtitle":[],"editor":[{"given":"Stacey","family":"Schultz-Cherry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,6,16]]},"references-count":58,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2020,6,16]]}},"alternative-id":["10.1128\/JVI.00195-20"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00195-20","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,16]]},"assertion":[{"value":"2020-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00195-20"}}