Dengue 2 virus inhibits in vitro megakaryocytic colony formation and induces apoptosis in thrombopoietin-inducible megakaryocytic differentiation from cord blood CD34+ cells

Basu, A.; Jain, P.; Gangodkar, S.V.; Shetty, S.; Ghosh, K.

Fems Immunology and Medical Microbiology 53(1): 46-51

2008


ISSN/ISBN: 0928-8244
PMID: 18371071
DOI: 10.1111/j.1574-695x.2008.00399.x
Accession: 030825008

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Abstract
Thrombocytopenia is frequently associated with dengue virus infection in humans. Although antiplatelet immunopathogenic processes have been implicated in the origin of dengue-associated thrombocytopenia, the effect of dengue viruses on megakaryocyte differentiation remains incompletely understood. In this study, we examined the effect of human dengue 2 virus isolates on the in vitro growth and differentiation of thrombopoietin-induced megakaryopoiesis of cord blood CD34+ cells. Dengue 2 viruses, but not Japanese encephalitis virus, showed a dose-dependent inhibition of CFU-Mk. Viral antigens could be detected by an immunohistochemical technique in 3-5% of the early megakaryocytic progenitors by the 5th postexposure day in liquid cultures with cell loss, increased annexin V binding and active caspase-3 expression. In summary, dengue 2 viruses can inhibit in vitro megakaryopoiesis, as well as infect and induce apoptotic cell death in a subpopulation of early megakaryocytic progenitors. These events might contribute towards the origin of thrombocytopenia in dengue disease.

Dengue 2 virus inhibits in vitro megakaryocytic colony formation and induces apoptosis in thrombopoietin-inducible megakaryocytic differentiation from cord blood CD34+ cells