Dengue 2 virus inhibits in vitro megakaryocytic colony formation and induces apoptosis in thrombopoietin-inducible megakaryocytic differentiation from cord blood CD34+ cells.
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.
Basu
Atanu
A
National Institute of Virology ICMR, Pune, India.
Jain
Preksha
P
Gangodkar
Shobha V
SV
Shetty
Shrimati
S
Ghosh
Kanjaksha
K
D018952:Antigens, CD34 / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003715:Dengue / Q000097:blood* / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D005312:Fetal Blood / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008533:Megakaryocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008858:Microscopy, Phase-Contrast; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology* / Q000821:virology; D013926:Thrombopoietin / Q000494:pharmacology*
D018952:Antigens, CD34; D013926:Thrombopoietin