Clark Kristina B, Hsiao Hui-Mien, Bassit Leda, Crowe James E, Schinazi Raymond F, Perng Guey Chuen, Villinger Francois
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA, USA.
Virology. 2016 Jun;493:162-72. doi: 10.1016/j.virol.2016.03.024. Epub 2016 Apr 6.
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.
巨核红细胞祖细胞(MEP)是登革病毒(DENV)在体内的潜在靶细胞;在登革病毒诱导的血小板减少症期间,已发现该病毒在体外与巨核细胞及血小板相关。我们在此报告,登革病毒2型(DENV2)能在人未分化的MEP细胞系(Meg01和K562)中良好繁殖。与在Vero细胞中繁殖的病毒相比,来自MEP细胞系的病毒具有相似的结构和浮力密度。然而,蛋白质印迹分析中不同的蛋白质模式提示了MEP-DENV2在稳定性和组成上的差异。此外,相对于Vero-DENV2,MEP-DENV2上包膜结构域I/II的抗体中和作用有所降低。在MEP细胞和Vero细胞中,传染性DENV2以相当的动力学和数量产生。然而,在MEP细胞的电子显微镜图像中出现的病毒粒子结构较少。我们提出,DENV2在巨核细胞中有效感染并产生病毒,且巨核细胞损伤可能有助于登革热疾病的发病机制。