title: N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement.
abstract: Dengue virus (DENV) NS1 is a versatile non-structural glycoprotein that is secreted as a hexamer, binds to the cell surface of infected and uninfected cells, and has immune evasive functions. DENV NS1 displays two conserved N-linked glycans at N130 and N207. In this study, we examined the role of these two N-linked glycans on NS1 secretion, stability, and function. Because some groups have reported reduced yields of infectious DENV when N130 and N207 are changed, we analyzed glycosylation-deficient NS1 phenotypes using a transgenic expression system. We show that the N-linked glycan at position 130 is required for stabilization of the secreted hexamer whereas the N-linked glycan at residue 207 facilitates secretion and extracellular protein stability. Moreover, NS1 mutants lacking an N-linked glycan at N130 did not interact efficiently with complement components C1s and C4. In summary, our results elucidate the contribution of N-linked glycosylation to the function of DENV NS1.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Pawit
authors.initials: P
authors.lastname: Somnuke
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hauhart
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Panisadee
authors.initials: P
authors.lastname: Avirutnan
mesh_terms: D003165:Complement System Proteins / Q000378:metabolism*; D003716:Dengue Virus / Q000145:classification / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D009154:Mutation; D011134:Polysaccharides; D012845:Sindbis Virus; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D017201:Virus Shedding
chemical_list: C079340:NS1 protein, Dengue virus type 2; D011134:Polysaccharides; D017361:Viral Nonstructural Proteins; D003165:Complement System Proteins