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Dengue virus nonstructural protein 1 is expressed in a glycosyl‐phosphatidylinositol‐linked form that is capable of signal transduction
Author(s) -
Jacobs Michael G.,
Robinson Peter J.,
Bletchly Cheryl,
Mackenzie Jason M.,
Young Paul R.
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.99-0829com
Subject(s) - biology , signal transduction , dengue virus , virus , microbiology and biotechnology , virology
Dengue virus nonstructural protein 1 (NS1) is expressed on the surface of infected cells and is a target of human antibody responses to dengue virus infection. We show here that dengue virus uses the cellular glycosyl‐phosphatidylinositol (GPI) linkage pathway to express a GPI‐anchored form of NS1 and that GPI anchoring imparts a capacity for signal transduction in response to binding of NS1‐specific antibody. This study is the first to identify GPI linkage of a virus‐encoded 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‐specific phospholipase C and by metabolic incorporation of the GPI‐specific components ethanolamine and inositol. In common with other GPI‐anchored proteins, addition of specific antibody resulted in signal transduction, as evidenced by tyrosine phosphorylation of cellular proteins. Antibody‐induced signal transduction by GPI‐linked NS1 suggests a mechanism of cellular activation that may contribute to the pathogenesis of human dengue disease. Signal transduction by a GPI‐anchored viral antigen interacting with a specific antibody that it induces is a new concept in the pathogenesis of viral disease.–Jacobs, M. G., Robinson, P. J., Bletchly, C., Mackenzie, J. M., Young, P. R. Dengue virus nonstructural protein 1 is expressed in a glycosylphosphatidyl‐inositol‐linked form that is capable of signal transduction FASEB J. 14, 1603–1610 (2000)