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We show here that dengue virus uses the cellular glycosyl\u2010phosphatidylinositol (GPI) linkage pathway to express a GPI\u2010anchored form of NS1 and that GPI anchoring imparts a capacity for signal transduction in response to binding of NS1\u2010specific antibody. This study is the first to identify GPI linkage of a virus\u2010encoded protein. The GPI anchor addition signal for NS1 was identified, by transfection of HeLa cells with dengue cDNA constructs, as a downstream hydrophobic domain in NS2A. GPI linkage of NS1 in both transfected and infected cells was demonstrated by cleavage of NS1 from the surface by PI\u2010specific phospholipase C and by metabolic incorporation of the GPI\u2010specific components ethanolamine and inositol. In common with other GPI\u2010anchored proteins, addition of specific antibody resulted in signal transduction, as evidenced by tyrosine phosphorylation of cellular proteins. Antibody\u2010induced signal transduction by GPI\u2010linked NS1 suggests a mechanism of cellular activation that may contribute to the pathogenesis of human dengue disease. Signal transduction by a GPI\u2010anchored viral antigen interacting with a specific antibody that it induces is a new concept in the pathogenesis of viral disease.\u2013Jacobs, M. G., Robinson, P. J., Bletchly, C., Mackenzie, J. M., Young, P. R. Dengue virus nonstructural protein 1 is expressed in a glycosylphosphatidyl\u2010inositol\u2010linked form that is capable of signal transduction\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 1603\u20131610 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fj.99-0829com","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T09:16:12Z","timestamp":1516266972000},"page":"1603-1610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":198,"title":["Dengue virus nonstructural protein 1 is expressed in a glycosyl\u2010phosphatidylinositol\u2010linked form that is capable of signal transduction"],"prefix":"10.1096","volume":"14","author":[{"given":"Michael G.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Paediatrics Imperial College School of Medicine Norfolk Place London W2 1PG U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Robinson","sequence":"additional","affiliation":[{"name":"MRC Clinical Sciences Centre Imperial College School of Medicine London W12 0NN U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Bletchly","sequence":"additional","affiliation":[{"name":"Sir Albert Sakzewski Virus Research Centre Royal Children's Hospital Brisbane Queensland 4029 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Sir Albert Sakzewski Virus Research Centre Royal Children's Hospital Brisbane Queensland 4029 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology University of Queensland Brisbane Queensland 4072 Australia"},{"name":"Sir Albert Sakzewski Virus Research Centre Royal Children's Hospital Brisbane Queensland 4029 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,8]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Report N117","author":"World Health Organisation","year":"1996"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9656"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.Supplement_4.S830"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.6.4226-4232.1997"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.4023707"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(82)90515-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(88)90406-0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1128\/jvi.63.8.3345-3352.1989","article-title":"In vitro processing of dengue virus structural proteins: cleavage of the pre\u2010membrane protein","volume":"63","author":"Markoff L.","year":"1989","journal-title":"J. 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