title: Multiploid CD61+ cells are the pre-dominant cell lineage infected during acute dengue virus infection in bone marrow.
abstract: Depression of the peripheral blood platelet count during acute infection is a hallmark of dengue. This thrombocytopenia has been attributed, in part, to an insufficient level of platelet production by megakaryocytes that reside in the bone marrow (BM). Interestingly, it was observed that dengue patients experience BM suppression at the onset of fever. However, few studies focus on the interaction between dengue virus (DENV) and megakaryocytes and how this interaction can lead to a reduction in platelets. In the studies reported herein, BM cells from normal healthy rhesus monkeys (RM) and humans were utilized to identify the cell lineage(s) that were capable of supporting virus infection and replication. A number of techniques were employed in efforts to address this issue. These included the use of viral RNA quantification, nonstructural protein and infectivity assays, phenotypic studies utilizing immunohistochemical staining, anti-differentiation DEAB treatment, and electron microscopy. Cumulative results from these studies revealed that cells in the BM were indeed highly permissive for DENV infection, with human BM having higher levels of viral production compared to RM. DENV-like particles were predominantly observed in multi-nucleated cells that expressed CD61+. These data suggest that megakaryocytes are likely the predominant cell type infected by DENV in BM, which provides one explanation for the thrombocytopenia and the dysfunctional platelets characteristic of dengue virus infection.
authors.affiliation: Department of Pathology and Laboratory Medicine & the Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Clark
authors.forename: Sansanee
authors.initials: S
authors.lastname: Noisakran
authors.forename: Nattawat
authors.initials: N
authors.lastname: Onlamoon
authors.forename: Hui-Mien
authors.initials: HM
authors.lastname: Hsiao
authors.forename: John
authors.initials: J
authors.lastname: Roback
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Guey Chuen
authors.initials: GC
authors.lastname: Perng
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000821:virology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000821:virology*; D019070:Cell Lineage / Q000502:physiology*; D003114:Colony-Forming Units Assay; D003715:Dengue / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008253:Macaca mulatta; D008533:Megakaryocytes / Q000378:metabolism / Q000821:virology; D013921:Thrombocytopenia / Q000378:metabolism / Q000821:virology; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D039661:Integrin beta3; C007368:C.I. Solvent Yellow 56; D010128:p-Aminoazobenzene