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The role of dengue virus nonstructural protein 1 (NS1) C‐terminal region in anti‐NS1‐mediated platelet dysfunction
Author(s) -
Lin YeeShin,
Chen MeiChun,
Lin ChiouFeng,
Anderson Robert,
Lei HuanYao
Publication year - 2008
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/fasebj.22.2_supplement.502
Subject(s) - platelet , antibody , epitope , chemistry , antigen , platelet activation , microbiology and biotechnology , immunology , virology , biology
Dengue virus (DV) infection may develop into severe hemorrhage. Our previous studies showed that anti‐DV nonstructural protein 1 (NS1) cross‐reacted with human platelets and inhibited platelet aggregation. Based on the sequence homology alignment, the C‐terminal region of DV NS1 protein contained cross‐reactive epitopes which are shared between NS1 and self‐antigens. To investigate the pathological roles of cross‐reactive epitopes of NS1, we compared the effects of antibodies against full‐length DV NS1 and NS1 lacking the C‐terminal amino acids 271 to 352 (ΔC NS1). We found that anti‐ΔC NS1 showed lower platelet binding ability than that of anti‐full‐length NS1. Anti‐full‐length NS1 but not anti‐ΔC NS1 inhibited platelet aggregation. Studies on the mechanism of platelet aggregation inhibition indicated an effect of anti‐DV NS1 antibodies on integrin activation. Using a murine model to assess the bleeding tendency caused by anti‐DV NS1, we found that the bleeding time in full‐length NS1‐hyperimmunized mice was longer than that in the normal control. ΔC NS1‐hyperimmunized mice showed a bleeding time similar to that of normal control mice. Passive immunization with anti‐DV NS1 antibodies showed a decrease in antibody titers which was correlated with the binding of antibodies to platelets in mice. This finding was not observed in mice given anti‐ΔC NS1. In conclusion, we demonstrated that platelet dysfunction and bleeding tendency were induced by anti‐full‐length DV NS1 but not by anti‐ΔC NS1 antibodies. These findings may provide a strategy for dengue vaccine development.