Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice. (J Virol. 87(21):11648-58.) 地點(room):601教室

報告日期: 2014/10/31
報告時間: 4:00/4:50
報告學生: Amrita VATS
講評老師: 林以行
附件下載: 下載[1435-1412237781-1.pdf] 

Inhibition of Megakaryocyte Development in the Bone Marrow Underlies Dengue Virus–Induced Thrombocytopenia in Humanized Mice

Aishwarya Sridharan,, Qingfeng Chen,,Kin Fai Tang,d Eng Eong Ooi, Martin L. Hibberd, Jianzhu Chen ..

Journal of Virology :Nov 2013 Vol .87 no 21. 11648-11658

Speaker: Amrita vats                             Time: 4:00- 4:50 PM Oct 31, 2014

Commentator: Prof Yee shin Lin                   Place: 601

Abstract

A characteristic clinical feature of dengue virus infection is thrombocytopenia,though its underlying mechanism is not definitely determined . Earlier findings suggest that DV may induce thrombocytopenia via direct interactions with megakaryocytes and platelets.DV has also been shown to reduce circulating platelets counts independent of virus attachment or entry into platelets or their precursors.In this study by adoptive transfer of human CD34+ fetal liver cells into immunodeficient mice,a humanized mice constructed with significant levels of human platelets ,monocytes/macrophages ,and hepatocytes.Infection of humanized  mice with both lab–adapted and clinical strains of dengue virus induces characteristics human hematological changes, including transient leukopenia and thrombocytopenia. Dengue 2 virus can inhibit in vitro megakayopoiesis as well as infect and induce apoptotic cell death in a subpopulation of early megakaryocytic progenitors. In earlier studies mice infected with DENV2 NGC & DENV-2 strain K0049 showed 2 peak distribution level upto 18 to 21 day p.i in spleen, BM and liver. It is showed in this study that the specific depletion of human platelets is not mediated by antibodies in the periphery or reduced production of human thrombopoietin in the liver but due to reduction of human megakaryocytes and megakaryocyte progenitors in the bone marrow of the infected mice .These findings identify inhibition of platelet production in the bone marrow as a key mechanism underlying dengue –induced thrombocytopenia and suggest the utility of the improved humanized mouse model in studying dengue virus infection and pathogenesis in a human cell context.

  1. Janvir Mota,Rebeca Rico-Hesse. Dengue virus Tropism in Humanizes Mice Recapitulates Human Dengue fever. Plos One: 2011.
  2. Wang S,He R Patarapotikul J,Innis BL,Anderson R.Antibody-enhanced binding of dengue-2 virus to human platelets .Virology; 1995; 213(1): 254-7
  3. Natalia Frias–Staheli ,Marcus Dorner,Svetlana Marukian et al.Utility of humanized BLT Mice for analysis of Dengue Virus Infection and Antiviral Drug Testing.JOV; 88(4):2205-2218.