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Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice.
J Thromb Haemost. 2007 Nov; 5(11):2291-9.JT

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+Show Affiliations

Sun DS
Institute of Molecular and Cellular Biology, Tzu-Chi University, Hualien, Taiwan.
King CC
No affiliation info available
Huang HS
No affiliation info available
Shih YL
No affiliation info available
Lee CC
No affiliation info available
Tsai WJ
No affiliation info available
Yu CC
No affiliation info available
Chang HH
No affiliation info available

MeSH

AnimalsAntibodies, ViralAutoantibodiesBlood PlateletsDengueDengue VirusHumansMiceMice, Inbred C57BLRabbitsThrombocytopeniaViral Nonstructural Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17958746

Citation

Sun, D-S, et al. "Antiplatelet Autoantibodies Elicited By Dengue Virus Non-structural Protein 1 Cause Thrombocytopenia and Mortality in Mice." Journal of Thrombosis and Haemostasis : JTH, vol. 5, no. 11, 2007, pp. 2291-9.
Sun DS, King CC, Huang HS, et al. Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice. J Thromb Haemost. 2007;5(11):2291-9.
Sun, D. S., King, C. C., Huang, H. S., Shih, Y. L., Lee, C. C., Tsai, W. J., Yu, C. C., & Chang, H. H. (2007). Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice. Journal of Thrombosis and Haemostasis : JTH, 5(11), 2291-9.
Sun DS, et al. Antiplatelet Autoantibodies Elicited By Dengue Virus Non-structural Protein 1 Cause Thrombocytopenia and Mortality in Mice. J Thromb Haemost. 2007;5(11):2291-9. PubMed PMID: 17958746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice. AU - Sun,D-S, AU - King,C-C, AU - Huang,H-S, AU - Shih,Y-L, AU - Lee,C-C, AU - Tsai,W-J, AU - Yu,C-C, AU - Chang,H-H, PY - 2007/10/26/pubmed PY - 2007/12/27/medline PY - 2007/10/26/entrez SP - 2291 EP - 9 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 5 IS - 11 N2 - 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. SN - 1538-7933 UR - https://www.unboundmedicine.com/medline/citation/17958746/Antiplatelet_autoantibodies_elicited_by_dengue_virus_non_structural_protein_1_cause_thrombocytopenia_and_mortality_in_mice_ DB - PRIME DP - Unbound Medicine ER -