title: Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice.
abstract: BACKGROUND
  The mechanisms responsible for thrombocytopenia associated with dengue fever (DF) and dengue hemorrhage fever (DHF) remain unclear.
  
  
  OBJECTIVE
  In this study, we investigated the pathogenic effects of dengue virus (DENV) non-structural protein 1 (NS1) on the elicitation of platelet cross-reactive antibodies.
  
  
  RESULTS
  The results showed that anti-DENV NS1 immunoglobulins (Igs) derived from both patients with DF/DHF and recombinant NS1-immunized rabbits could opsonize normal human platelets and enhance platelet-macrophage engagements in vitro. In addition, treatments with anti-NS1 Igs abnormally activated human platelets and induced thrombocytopenia in mice. These prothrombotic characteristics of anti-NS1 Ig might increase the disease burden of coagulant-aberrant DHF patients. To test this hypothesis, we injected anti-NS1 Igs into C57BL/6J mice that were preconditioned into a hypercoagulable state by warfarin treatments. When given before but not after platelet-lysate pre-adsorption, the anti-NS1 Igs injection treatments significantly increased mortality, fibrin deposition in lung, and plasma D-dimer levels, but significantly decreased anticoagulant proteins C, protein S and antithrombin III.
  
  
  CONCLUSIONS
  These results suggest that the platelet-bound antibody fractions of anti-NS1 Ig are prothrombotic, which might exacerbate the severity of disease in hosts with an imbalanced coagulant system.
authors.affiliation: Institute of Molecular and Cellular Biology, Tzu-Chi University, Hualien, Taiwan.
authors.forename: D-S
authors.initials: DS
authors.lastname: Sun
authors.forename: C-C
authors.initials: CC
authors.lastname: King
authors.forename: H-S
authors.initials: HS
authors.lastname: Huang
authors.forename: Y-L
authors.initials: YL
authors.lastname: Shih
authors.forename: C-C
authors.initials: CC
authors.lastname: Lee
authors.forename: W-J
authors.initials: WJ
authors.lastname: Tsai
authors.forename: C-C
authors.initials: CC
authors.lastname: Yu
authors.forename: H-H
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000009:adverse effects; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology*; D001792:Blood Platelets / Q000276:immunology*; D003715:Dengue / Q000150:complications / Q000401:mortality*; D003716:Dengue Virus / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D013921:Thrombocytopenia / Q000209:etiology* / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D017361:Viral Nonstructural Proteins