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

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 CD341 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.

IUse of Mean platelet Volume as an initial diagnostic marker in evaluation of dengue fever

“…[14] Ghosh et al showed that DV-2 may directly interact with and activate platelets and thus may be responsible for thrombocytopenia. [15] This study may explain the findings of the present study with MPV being significantly higher in cases of dengue fever when compared to controls due to the activation of platelets causing a rise in MPV.…”

Clinical Profile of Dengue Infection in Pediatric Age Group in West India

“…[13] Dengue virus -2 induces apoptotic cell death in a subpopulation of early megakaryocytic progenitors which may contribute to thrombocytopenia in dengue disease. [14] Twenty two cases associated with neurological involvement. The incidence of neurological manifestations in patients diagnosed with Dengue Haemorrhagic Fever (DHF) and severe Dengue has been documented to vary from 3% (24/858) in prospective DHF studies to 25% in retrospective studies.…”

Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer?

“…Thrombocytopenia is also associated with DENV infection (de Azeredo et al 2015). Studies have reported increased thrombopoietin (TPO) levels in the blood of DENV-infected individuals (Matondang et al 2004), and that DENV inhibits TPO-inducible megakaryocyte differentiation from CD34+ cord blood cells in vitro (Basu et al 2008; Murgue et al 1997; Nakao et al 1989). Some reports also indicate increased clearance of circulating platelets either by platelet consumption due to coagulopathy or via activation of the complement system or by formation of anti-platelet antibodies by molecular mimicry (Alonzo et al 2012; Honda et al 2009; Lin et al 2001; Lin et al 2011; Srichaikul et al 1989).…”