{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T13:38:03Z","timestamp":1793972283753,"version":"4.8.0"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-001"},{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-009"},{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01 AI111598"],"award-info":[{"award-number":["U01 AI111598"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002784","name":"Canada Excellence Research Chairs, Government of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Influenza A viruses cause a spectrum of responses, from mild coldlike symptoms to severe respiratory illness and death. Intrinsic host factors, such as age, can influence disease severity. Glycosylation plays a critical role in influenza pathogenesis; however, the molecular drivers of influenza outcomes remain unknown. In this work, we characterized the host glycomic response to the H1N1 2009 pandemic influenza A virus (H1N1pdm09) as a function of age-dependent severity in a ferret model. Using our dual-color lectin microarray technology, we examined baseline glycosylation and glycomic response to infection in newly weaned and aged animals, models for young children and the elderly, respectively. Compared to adult uninfected ferrets, we observed higher levels of \u03b1-2,6-sialosides, the receptor for H1N1pdm09, in newly weaned and aged animals. We also observed age-dependent loss of O-linked \u03b1-2,3-sialosides. The loss of these highly charged groups may impact viral clearance by mucins, which corresponds to the lower clearance rates observed in aged animals. Upon infection, we observed dramatic changes in the glycomes of aged animals, a population severely impacted by the virus. In contrast, no significant alterations were observed in the newly weaned animals, which show mild to moderate responses to the H1N1pdm09. High mannose, a glycan recently identified as a marker of severity in adult animals, increased with severity in the aged population. However, the response was delayed, in line with the delayed development of pneumonia observed. Overall, our results may help explain the differential susceptibility to influenza A infection and severity observed as a function of age.<\/jats:p>","DOI":"10.1021\/acs.jproteome.0c00455","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:03:43Z","timestamp":1601251423000},"page":"4486-4495","source":"Crossref","is-referenced-by-count":17,"title":["Age-Dependent\nGlycomic Response to the 2009 Pandemic\nH1N1 Influenza Virus and Its Association with Disease Severity"],"prefix":"10.1021","volume":"19","author":[{"given":"Shuhui","family":"Chen","sequence":"first","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kasper","sequence":"additional","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai , , , ,","place":["New York, New York, United States, 10029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren P.","family":"Lashua","sequence":"additional","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted M.","family":"Ross","sequence":"additional","affiliation":[{"name":"University of Georgia , , , ,","place":["Athens, Georgia, United States, 30602"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Ghedin","sequence":"additional","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]},{"name":"NIAID\/NIH , , , ,","place":["Bethesda, Maryland, United\nStates, 20894"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4791-8524","authenticated-orcid":true,"given":"Lara K.","family":"Mahal","sequence":"additional","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]},{"name":"University of Alberta , , , ,","place":["Edmonton, AB, Canada, T6G 2G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"issue":"10127","key":"2026081714254969500_cit1","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates\nof global seasonal influenza-associated respiratory mortality: a modelling\nstudy","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"issue":"8","key":"2026081714254969500_cit2","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/nrmicro2613","article-title":"Influenza\nA viruses: new research developments","volume":"9","author":"Medina","year":"2011","journal-title":"Nat. Rev.\nMicrobiol."},{"issue":"7","key":"2026081714254969500_cit3","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1056\/NEJMoa0904023","article-title":"Severe respiratory\ndisease concurrent with the circulation of H1N1 influenza","volume":"361","author":"Chowell","year":"2009","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"2026081714254969500_cit4","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.virol.2010.02.020","article-title":"Modeling\nhost responses in ferrets\nduring A\/California\/07\/2009 influenza infection","volume":"401","author":"Rowe","year":"2010","journal-title":"Virology"},{"issue":"24","key":"2026081714254969500_cit5","doi-asserted-by":"publisher","first-page":"13187","DOI":"10.1128\/JVI.01456-12","article-title":"Differential pathological\nand immune responses in newly weaned ferrets are associated with a\nmild clinical outcome of pandemic 2009 H1N1 infection","volume":"86","author":"Huang","year":"2012","journal-title":"J. Virol"},{"issue":"12","key":"2026081714254969500_cit6","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1016\/j.ajpath.2019.08.017","article-title":"Age-Related\nPathology Associated with H1N1 A\/California\/07\/2009 Influenza Virus\nInfection","volume":"189","author":"Bissel","year":"2019","journal-title":"Am. J. Pathol."},{"issue":"5","key":"2026081714254969500_cit7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1242\/dmm.007823","article-title":"The ferret\nas a model organism to\nstudy influenza A virus infection","volume":"4","author":"Belser","year":"2011","journal-title":"Dis. Models\n& Mech."},{"issue":"3","key":"2026081714254969500_cit8","doi-asserted-by":"publisher","first-page":"e1003223","DOI":"10.1371\/journal.ppat.1003223","article-title":"Glycomic analysis of human respiratory\ntract tissues and correlation with influenza virus infection","volume":"9","author":"Walther","year":"2013","journal-title":"PLoS Pathog."},{"issue":"41","key":"2026081714254969500_cit9","doi-asserted-by":"publisher","first-page":"28489","DOI":"10.1074\/jbc.M114.588541","article-title":"Glycomic characterization of respiratory\ntract tissues of ferrets: implications for its use in influenza virus\ninfection studies","volume":"289","author":"Jia","year":"2014","journal-title":"J. Biol. 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Infect. Dis."},{"issue":"6","key":"2026081714254969500_cit19","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/cbic.200400403","article-title":"Development of a\nlectin microarray for the rapid analysis of protein glycopatterns","volume":"6","author":"Pilobello","year":"2005","journal-title":"ChemBioChem"},{"issue":"10","key":"2026081714254969500_cit20","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.1021\/pr200434y","article-title":"Identification of a conserved glycan signature for\nmicrovesicles","volume":"10","author":"Batista","year":"2011","journal-title":"J. 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Dis."},{"issue":"303","key":"2026081714254969500_cit25","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2566-7","article-title":"Host susceptibility\nto severe influenza A virus infection","volume":"23","author":"Clohisey","year":"2019","journal-title":"Crit.\nCare"},{"issue":"7","key":"2026081714254969500_cit26","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz225","article-title":"Age-Related Differences in Hospitalization\nRates, Clinical Presentation,\nand Outcomes Among Older Adults Hospitalized With Influenza-U.S. Influenza\nHospitalization Surveillance Network (FluSurv-NET)","volume":"6","author":"Czaja","year":"2019","journal-title":"Open Forum Infect. Dis."},{"issue":"3","key":"2026081714254969500_cit27","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1128\/JVI.06034-11","article-title":"Elicitation\nof anti-1918\ninfluenza virus immunity early in life prevents morbidity and lower\nlevels of lung infection by 2009 pandemic H1N1 influenza virus in\naged mice","volume":"86","author":"Giles","year":"2012","journal-title":"J. Virol"},{"issue":"10","key":"2026081714254969500_cit28","doi-asserted-by":"publisher","first-page":"5515","DOI":"10.1128\/JVI.07085-11","article-title":"Influenza virus H1N1pdm09 infections\nin the young and old: evidence of greater antibody diversity and affinity\nfor the hemagglutinin globular head domain (HA1 Domain) in the elderly\nthan in young adults and children","volume":"86","author":"Verma","year":"2012","journal-title":"J. Virol"},{"issue":"11","key":"2026081714254969500_cit29","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1128\/CVI.05357-11","article-title":"High incidence of severe influenza among individuals\nover 50 years of age","volume":"18","author":"Zhang","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"issue":"1","key":"2026081714254969500_cit30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1186\/s12879-018-3181-y","article-title":"Distribution of\ninfluenza virus types by age using case-based global surveillance\ndata from twenty-nine countries, 1999\u20132014","volume":"18","author":"Caini","year":"2018","journal-title":"BMC Infect. Dis."},{"issue":"8","key":"2026081714254969500_cit31","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1093\/glycob\/cwy052","article-title":"Streptococcal Siglec-like\nadhesins recognize different subsets of human plasma glycoproteins:\nimplications for infective endocarditis","volume":"28","author":"Bensing","year":"2018","journal-title":"Glycobiology"},{"issue":"5","key":"2026081714254969500_cit32","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1042\/BST20170402","article-title":"Mucins: the frontline defence of the lung","volume":"46","author":"Ridley","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"2026081714254969500_cit33","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/B978-0-12-407697-6.00004-0","article-title":"Cellular and molecular\nbiology of airway mucins","volume":"303","author":"Lillehoj","year":"2013","journal-title":"Int. Rev. Cell Mol.\nBiol."},{"issue":"23","key":"2026081714254969500_cit34","doi-asserted-by":"publisher","first-page":"12643","DOI":"10.1073\/pnas.1921962117","article-title":"Membrane-tethered\nmucin-like polypeptides sterically inhibit binding and slow fusion\nkinetics of influenza A virus","volume":"117","author":"Delaveris","year":"2020","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"issue":"2","key":"2026081714254969500_cit35","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.chom.2016.01.001","article-title":"The Interaction between\nRespiratory Pathogens and Mucus","volume":"19","author":"Zanin","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"43","key":"2026081714254969500_cit36","doi-asserted-by":"publisher","first-page":"E10089","DOI":"10.1073\/pnas.1805425115","article-title":"XBP1s activation\ncan globally remodel N-glycan structure distribution patterns","volume":"115","author":"Wong","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"10","key":"2026081714254969500_cit37","doi-asserted-by":"publisher","first-page":"9345","DOI":"10.1074\/jbc.M411122200","article-title":"Isolation\nand characterization of griffithsin, a novel HIV-inactivating protein,\nfrom the red alga Griffithsia sp","volume":"280","author":"Mori","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"4","key":"2026081714254969500_cit38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1750-2659.2011.00304.x","article-title":"Influenza\nneuraminidase","volume":"6","author":"Air","year":"2012","journal-title":"Influenza Other Respir. 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Perinatol."},{"issue":"1","key":"2026081714254969500_cit43","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1097\/MOP.0b013e3283350317","article-title":"Update\non the 2009 pandemic influenza A H1N1 in children","volume":"22","author":"Halasa","year":"2010","journal-title":"Curr. Opin. Pediatr."}],"container-title":["Journal of\nProteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.0c00455","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/19\/11\/4486\/14424801\/pr0c00455.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/19\/11\/4486\/14424801\/pr0c00455.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:03:30Z","timestamp":1786993410000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/19\/11\/4486\/1383711\/Age-Dependent-Glycomic-Response-to-the-2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,28]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,9,28]]},"published-print":{"date-parts":[[2020,11,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.0c00455","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.22.165613","asserted-by":"object"}]},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,28]]}}}