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

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

 J. Virol. November 2013 vol. 87 no. 21 11648-11658

Speaker: Andy D. Y. Hu (胡敦堯)                                 Time: 15:10~16:00, Oct. 22, 2014

Commentator: Dr. Ching-Chuan Liu (劉清泉 醫師)          Place: Room 602

Abstract:

    Dengue is an infectious disease spread through mosquito vectors and clinical symptoms of dengue virus (DENV) infection is usually accompanied with hematological changes [1]. A characteristic clinical feature of dengue virus infection is thrombocytopenia. To understand the cause of platelet drop during dengue disease, the authors constructed humanized mice (humice) by transplanting human CD34⁺ fetal liver cells into immunodeficient mice that develop human platelets, monocytes/macrophages, and hepatocytes. They infected these humice with lab-adopted and clinical strains of dengue virus serotype 2 (DENV2), and clinical symptoms of dengue infection in human were recaptured, which include leukopenia and thrombocytopenia. As a result, the authors found that depletion of human platelets is not due to antibody-mediated clearance or lacking of human thrombopoietin (TPO), which is the major cytokine that drives the differentiation of progenitor cells to megakaryocyte [2] and is mainly produced by hepatocytes in liver [3], but instead is due to inhibition of producing human megakaryocytes and their progenitor cells in bone marrow of the infected mice. Results from this study suggesting that the inhibition of platelet production in bone marrow may be a key mechanism of thrombocytopenia caused by dengue infection.

 Reference

1.     World Health Organization. 2009. Dengue guidelines for diagnosis treatment prevention and control. World Health Organization, Geneva, Switzerland.

2.     Avecilla ST, Hattori K, Heissig B, Tejada R,and Rafii S. 2004. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required forthrombopoiesis. Nat. Med. 10:64–71.

3.     Wolber EM, Jelkmann W. 2002. Thrombopoietin: the novel hepatichormone. News Physiol. Sci. 17:6–10.