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Abstract
Dengue viruses (DEN) which belong to the genus Flavivirus of the family Flaviviridae are transmitted by Aedes mosquitoes. They are subgrouped into four serotypes, DEN 1, 2, 3 and 4. Infection with DEN is associated with a wide range of clinical severity, from mild febrile illness as dengue fever (DF) to life-threatening diseases including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The mechanisms involved in the pathogenesis of DHF/DSS remain unclear although some plausible explanations have been proposed. In this study, the anti-NS1 antibodies present in patient and immune murine sera are determined, and their reactivities with platelets are also detected. Both DHF/DSS and DF patients possess high anti-NS1 IgG titers in their sera. The anti-NS1 IgM titers are varied. Interestingly, dengue patient sera cross-react with platelets and these anti-platelet autoantibodies belong to IgM but not IgG isotype. In contrast, in the NS1-immunized mice, the isotype of anti-platelet autoantibodies is IgG. The neutralization experiments by pretreatment of sera with recombinant NS1 indicate that the anti-platelet antibodies are, at least in part, reactive with NS1. The functional study of the anti-platelet antibodies shows an inhibition on ADP-induced platelet aggregation. By Western blot analysis using anti-NS1 antibodies, we found two protein bands present on the platelet membrane components with molecular weights around 60 kDa. One of the peptides was sequenced showing N-terminal amino acids of DNQKQQVALGFLDYV which is similar to some ATP/GTP binding proteins associated with platelet aggregation. These results show that some epitopes on NS1 may cause hemostatic abnormalities. To provide a more satisfactory and protective dengue vaccine candidate, a strategy may be proceeded by deleting or mutating the epitopes that cause the pathogenic effects.
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