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Extracellular NS1 has been shown to modulate the complement system and to enhance DENV infection, yet its structure and function remain essentially unknown. By combining cryoelectron microscopy analysis with a characterization of NS1 amphipathic properties, we show that the secreted NS1 hexamer forms a lipoprotein particle with an open-barrel protein shell and a prominent central channel rich in lipids. Biochemical and NMR analyses of the NS1 lipid cargo reveal the presence of triglycerides, bound at an equimolar ratio to the NS1 protomer, as well as cholesteryl esters and phospholipids, a composition evocative of the plasma lipoproteins involved in vascular homeostasis. This study suggests that DENV NS1, by mimicking or hijacking lipid metabolic pathways, contributes to endothelium dysfunction, a key feature of severe dengue disease.<\/jats:p>","DOI":"10.1073\/pnas.1017338108","type":"journal-article","created":{"date-parts":[[2011,4,25]],"date-time":"2011-04-25T23:05:55Z","timestamp":1303772755000},"page":"8003-8008","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":312,"title":["Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein"],"prefix":"10.1073","volume":"108","author":[{"given":"Irina","family":"Gutsche","sequence":"first","affiliation":[{"name":"Laboratoire de Virologie Mol\u00e9culaire et Structurale, Centre National de la Recherche Scientifique, Unit\u00e9 Propre de Recherche 3296, F-91198 Gif-sur-Yvette, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fass\u00e9li","family":"Coulibaly","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie Mol\u00e9culaire et Structurale, Centre National de la Recherche Scientifique, Unit\u00e9 Propre de Recherche 3296, F-91198 Gif-sur-Yvette, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Voss","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Virologie Structurale, Institut Pasteur, F-75015 Paris, France;"},{"name":"D\u00e9partement de Virologie, Institut Pasteur, F-75015 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 de Recherche Associ\u00e9e 3015, F-75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Salmon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"d'Alayer","sequence":"additional","affiliation":[{"name":"Plate-Forme d'Analyse et de Micros\u00e9quen\u00e7age des Prot\u00e9ines, Institut Pasteur, F-75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Ermonval","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Virologie, Institut Pasteur, F-75015 Paris, France;"},{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire des Bunyavirus, Institut Pasteur, F-75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Larquet","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biologie Structurale, Institut de Min\u00e9ralogie et de Physique des Milieux Condens\u00e9s, Unit\u00e9 Mixte de Recherche 7590, Centre National de la Recherche Scientifique, Universit\u00e9 Pierre et Marie Curie Paris VI, F-75252 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Charneau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Virologie, Institut Pasteur, F-75015 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 de Recherche Associ\u00e9e 3015, F-75015 Paris, France;"},{"name":"Laboratoire de Virologie Mol\u00e9culaire et de Vectorologie, Institut Pasteur, F-75015 Paris, France; 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