Characterization of dengue virus 2 growth in megakaryocyte-erythrocyte progenitor cells

• Type of Material: Article
• Authors: Kristina B. Clark, Emory University; Hui-Mien Hsiao, Emory University; Leda Bassit, Emory University; James E. Crowe, Vanderbilt University; Raymond Schinazi, Emory University; Guey Chuen Perng, National Cheng Kung University; Francois Villinger, Emory University
• Language: English
• Date: 2016-06
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2016.03.024
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 493
• Start Page: 162
• End Page: 172
• Grant/Funding Information: This research received no specific grant from any funding agency in the public, commercial, or nonprofit sector.; RFS is supported in part from the Department of Veterans Affairs.
• Keywords: Megakaryocyte; MEP; TICK-BORNE ENCEPHALITIS; Virology; Dengue virus; HUMAN-MONOCYTES; MOSQUITO CELLS; Science & Technology; HUMAN DENDRITIC CELLS; IN-VITRO; Meg01; Electron microscopy; Erythrocyte; PARTICLE; Life Sciences & Biomedicine; E-PROTEIN; INFECTION; Progenitor; CYTOKINE PRODUCTION; HEMORRHAGIC-FEVER; K562
• Research Categories: Biology, Virology; Health Sciences, Immunology; Biology, Microbiology

Abstract

Megakaryocyte-erythrocyte progenitor (MEP) cells are potential in vivo targets of dengue virus (DENV); the virus has been found associated with megakaryocytes ex vivo and platelets during DENV-induced thrombocytopenia. We report here that DENV serotype 2 (DENV2) propagates well in human nondifferentiated MEP cell lines (Meg01 and K562). In comparison to virus propagated in Vero cells, viruses from MEP cell lines had similar structure and buoyant density. However, differences in MEP-DENV2 stability and composition were suggested by distinct protein patterns in western blot analysis. Also, antibody neutralization of envelope domain I/II on MEP-DENV2 was reduced relative to that on Vero-DENV2. Infectious DENV2 was produced at comparable kinetics and magnitude in MEP and Vero cells. However, fewer virion structures appeared in electron micrographs of MEP cells. We propose that DENV2 infects and produces virus efficiently in megakaryocytes and that megakaryocyte impairment might contribute to dengue disease pathogenesis.