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In this study, we demonstrate that the virus strains that differ in the degree of N\u2010linked glycosylation on the globular head of their hemagglutinin glycoprotein also differed in their (i) sensitivity to neutralization by a mannose\u2010specific lectin in mouse lung fluids and (ii) ability to infect (and, therefore, to be destroyed) by airway macrophages. Virus strain BJx109 (H3N2), but not PR8 (H1N1), was sensitive to neutralization by mouse lung fluids and infected airway macrophages efficiently <jats:italic>in vitro<\/jats:italic> and these antiviral activities were blocked by mannan, a complex polymer of mannose residues. Although intranasal (i.n.) infection of mice with PR8 led to severe disease and mortality, mice infected with an equivalent dose of BJx109 displayed no signs of disease. However, i.n. treatment of BJx109\u2010infected mice with mannan led to viral pneumonia, severe disease and death characterized by excessive virus replication, pulmonary inflammation, vascular leak and lung edema. Thus, when mannose\u2010specific innate defences were inhibited <jats:italic>in vivo<\/jats:italic>, virus strain BJx109 induced severe viral pneumonia similar to that of PR8. Together, these findings highlight the importance of N\u2010linked glycans as a target for recognition and destruction of influenza viruses by the innate immune system. Moreover, soluble and cell\u2010associated lectins coordinate to modulate disease severity following influenza virus infection of mice.<\/jats:p>","DOI":"10.1038\/icb.2010.113","type":"journal-article","created":{"date-parts":[[2010,10,12]],"date-time":"2010-10-12T09:41:03Z","timestamp":1286876463000},"page":"482-491","source":"Crossref","is-referenced-by-count":19,"title":["Inhibition of lectin\u2010mediated innate host defences <i>in vivo<\/i> modulates disease severity during influenza virus infection"],"prefix":"10.1111","volume":"89","author":[{"given":"Michelle D","family":"Tate","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew G","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick C","family":"Reading","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne  Parkville Victoria Australia"},{"name":"WHO Collaborating Centre for Reference and Research on Influenza  North Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,10,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.531"},{"key":"e_1_2_8_2_1","volume-title":"Fields Virology","author":"Wright PF","year":"2001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.352"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/289373a0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01310484"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.11.8377-8384.1997"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.12.4485"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.63.8.3296-3300.1989"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(01)00389-6"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510449"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1997.273.6.L1156"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.11.8204-8212.1997"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-007-0983-4"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5868"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00769-07"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8565-8572.2004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.11.5190-5197.2000"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00142.2004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.279.3.L468"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.43.28438"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(82)90135-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.31.2.751-757.1981"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.22.3.758-762.1978"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(11)80365-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.12.9450-9457.1997"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.23.14933-14944.2005"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535710"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00845a033"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11259-009-9307-3"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02677-05"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05495"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11772-7"},{"key":"e_1_2_8_33_1","first-page":"1009","article-title":"Polymorphonuclear leukocytes as a significant source of tumor necrosis factor\u2010alpha in endotoxin\u2010challenged lung tissue","volume":"143","author":"Xing Z","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_8_34_1","first-page":"1082","article-title":"Glycoproteins as influenza virus hemagglutinin inhibitors and as cellular receptors","author":"Gottschalk A","year":"1972","journal-title":"In Glycoproteins. 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