Role of CD61+ cells in thrombocytopenia of dengue patients

• Type of Material: Article
• Authors: Sansanee Noisakran, Emory University; Nattawat Onlamoon, Mahidol University; Kovit Pattanapanyasat, Mahidol University; Hui-Mien Hsiao, Emory University; Pucharee Songprakhon, Mahidol University; Nasikarn Angkasekwinai, Mahidol University; Kulkanya Chokephaibulkit, Mahidol University; Francois Villinger, Emory University; Aftab A Ansari, Emory University; Guey Chuen 'Oscar' Perng, Emory University
• Language: English
• Date: 2012-11
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Japanese Society of Hematology 2012
• Final Published Version (URL): http://link.springer.com/article/10.1007%2Fs12185-012-1175-x
• Title of Journal or Parent Work: International Journal of Hematology
• ISSN: 0925-5710
• Volume: 96
• Issue: 5
• Start Page: 600
• End Page: 610
• Grant/Funding Information: The research was supported in part by Emory SOM start-up fund, Thailand Research Fund for Senior Research Scholar, Robert E. Shop International Fellowship, the U19 Pilot Project Funds U19 AI057266 (RFA-AI-02-042), NIH/SERCEB, Emory URC grants, and the NCRR p51 support to the Yerkes National Primate Research Center DRR000165.
• Keywords: Fever; Dengue; Thrombocytopenia; DHF; DF; Megakaryocytes; Viremia
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Although hematological disorders with salient features of thrombocytopenia have been well documented in dengue patients, the role of CD61-expressing platelets and the megakaryocytic cell lineage in the pathogenesis of dengue virus (DENV) infection remains largely unexplored. A prospective observational study was performed using blood samples and PBMCs from dengue-confirmed patients, as well as from rhesus monkeys (RM) experimentally infected with DENV. Immunohistochemical staining and FACS techniques were applied to evaluate the frequencies of CD61+ cells that contained DENV antigen. Highly enriched population of CD61+ cells was also isolated from acute DENV-infected RM and assayed for DENV RNA by quantitative RT-PCR. Results revealed that DENV antigen was found in small vesicles of varying size, and more frequently in anucleated cells associated with platelets in dengue patients. The DENV antigen-containing cells were CD61+ and appeared to share characteristics of megakaryocytes. Kinetic profiles of CD61+ cells from DENV-infected RM revealed a transient increase in CD61+CD62P+ cells early after DENV infection. DENV RNA in a highly enriched population of CD61+cells from the infected RM was observed during acute stage. Our results indicate that virus containing CD61+ cells may be directly linked to the platelet dysfunction and low platelet count characteristics of dengue patients.