Infection of bone marrow cells by dengue virus in vivo

• Type of Material: Article
• Authors: Sansanee Noisakran, Emory University; Nattawat Onlamoon, Emory University; Hui-Mien Hsiao, Emory University; Kristina B. Clark, Emory University; Francois Villinger, Emory University; Aftab A Ansari, Emory University; Guey Chuen 'Oscar' Perng, Emory University
• Language: English
• Date: 2012-03
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016%2Fj.exphem.2011.11.011
• Title of Journal or Parent Work: Experimental Hematology
• ISSN: 0301-472X
• Volume: 40
• Issue: 3
• Start Page: 250
• End Page: 259.e4
• 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/Southeastern Regional Center of Excellence for Emerging Infections and Biodefense, Emory University Research Committee grants, Howard Hughes Medical Institute Med into Grad Initiative (KBC), and the NCRR p51 support to the Yerkes National Primate Research Center DRR000165.
• Research Categories: Health Sciences, Pathology

Abstract

Abnormal bone marrow (BM) suppression is one of the hallmarks of dengue virus (DENV) infection in patients. Although the etiology remains unclear, direct viral targeting of the BM has been reasoned to be a contributing factor. The present studies were carried out in an effort to determine the potential effect of DENV infection on the cellularity of BM using a previously established nonhuman primate model of DENV-induced coagulopathy. BM aspirates were collected at various times from the infected nonhuman primate and cells were phenotypically defined and isolated using standard flow cytometry (fluorescence-activated cell sorting). These isolated cells were subjected to detection of DENV utilizing quantitative real-time reverse transcription polymerase chain reaction, electron microscopy, and immunostaining techniques. DENV RNA was detectable by quantitative real-time reverse transcription polymerase chain reaction in BM specimens and the presence of DENV-like particles within platelet was confirmed by electron microscopy. Enumeration of BM cells revealed a transient surge in cellularity at day 1, followed by a gradual decline from days 2 to 10 post infection. Detailed phenotypic studies showed similar kinetics in the frequencies of CD41+CD61+ cells, regardless of CD34 and CD45 expression. The CD61+ cells were not only the predominant cells that stained for DENV antigen but fluorescence-activated cell sorting–assisted isolation of CD61+ cells from the BM were shown to contain infectious DENV by coculture with Vero cells. These data support the view that intravenous infection of nonhuman primate with DENV leads to direct infection of the BM, which is likely to be a contributing factor for transient cell suppression in the peripheral blood characteristic of acute DENVinfection.