Multiploid CD61+ Cells Are the Pre-Dominant Cell Lineage Infected during Acute Dengue Virus Infection in Bone Marrow

• Type of Material: Article
• Authors: Kristina B. Clark, Emory University; Sansanee Noisakran, National Science and Technology Development Agency; Nattawat Onlamoon, Mahidol University; Hui-Mien Hsiao, Emory University; John D Roback, Emory University; Francois Villinger, Emory University; Aftab A Ansari, Emory University; Guey Chuen 'Oscar' Perng, Emory University
• Language: English
• Date: 2012-12-27
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Clark et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052902
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 12
• Start Page: e52902
• End Page: e52902
• Grant/Funding Information: The research was supported in part by the U19 Pilot Project Funds U19 AI057266 (RFA-AI-02-042), National Institutes of Health/SERCEB, Emory URC grants, HHMI Grad-into-Med program fund, the NCRR p51 support to the Yerkes National Primate Research Center DRR000165, and the National Science Council (NSC99-2321-B006-008) with the Center of Infectious Disease and Signaling Research, NCKU, Taiwan.
• Research Categories: Health Sciences, Pathology

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.