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One of the most important clinical signs of dengue virus infection is the reduction of white blood cells and platelets in human peripheral blood (leukopenia and thrombocytopenia, respectively), which may significantly impair the clearance of dengue virus by the immune system. The cause of thrombocytopenia and leukopenia during dengue infection is still unknown, but may be related to severe suppression of bone marrow populations including hematopoietic stem cells and megakaryocytes, the progenitors of white blood cells and platelets respectively. Here, we explored the possibility that bone marrow suppression, including ablation of megakaryocyte populations, is caused by dengue virus infection of megakaryocytes. We used three different models to measure dengue virus infection and replication: in vitro, in a human megakaryocyte cell line with viral receptors, ex vivo, in primary human megakaryocytes, and in vivo, in humanized mice. All three systems support dengue virus infection and replication, including virus strains from serotypes 1, 2, and 3, and clinical signs, in vivo; all assays showed viral RNA and/or infectious viruses 7-14 days post-infection. Although we saw no significant decrease in cell viability in vitro, there was significant depletion of mature megakaryocytes in vivo. We conclude that megakaryocytes can produce dengue viruses in the bone marrow niche, and a reduction of cell numbers may affect bone marrow homeostasis.
This article was published in the following journal.
Name: PLoS neglected tropical diseases
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An acute infectious, eruptive, febrile disease caused by four antigenically related but distinct serotypes of the DENGUE VIRUS. It is transmitted by the bite of infected Aedes mosquitoes, especially A. aegypti. Classical dengue (dengue fever) is self-limiting and characterized by fever, myalgia, headache, and rash. DENGUE HEMORRHAGIC FEVER is a more virulent form of dengue virus infection and a separate clinical entity. (From Dorland, 28th ed)
A distinct and virulent form of DENGUE characterized by thrombocytopenia and hemoconcentration (grades I and II) and distinguished by a positive tourniquet test. When accompanied by circulatory failure and shock (grades III and IV), it is called dengue shock syndrome. (From Dorland, 28th ed)
Circular, double-stranded DNA viruses that invade giant DNA viruses (GIANT VIRUSES) which infect eukaryotes.
A virulent form of dengue characterized by THROMBOCYTOPENIA and an increase in vascular permeability (grades I and II) and distinguished by a positive pain test (e.g., TOURNIQUET PAIN TEST). When accompanied by SHOCK (grades III and IV), it is called dengue shock syndrome.
DNA viruses that have genomes up to several megabases in length and infect primarily single-celled EUKARYOTES.
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