Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Dental School Building, Room 429, 1462 Clifton Road, Atlanta, GA 30322, USA.
Int J Hematol. 2012 Nov;96(5):600-10. doi: 10.1007/s12185-012-1175-x. Epub 2012 Sep 18.
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.
虽然已有文献充分记载了登革热患者存在以血小板减少为突出特征的血液系统疾病，但 CD61 表达血小板和巨核细胞系在登革热病毒（DENV）感染发病机制中的作用在很大程度上仍未得到探索。本前瞻性观察性研究使用了来自确诊登革热患者以及经 DENV 实验感染的恒河猴（RM）的血液样本和 PBMCs。采用免疫组织化学染色和 FACS 技术评估了含有 DENV 抗原的 CD61(+)细胞的频率。还从急性 DENV 感染的 RM 中分离出高度富集的 CD61(+)细胞，并通过定量 RT-PCR 检测 DENV RNA。结果表明，DENV 抗原存在于不同大小的小泡中，在与血小板相关的无核细胞中更为常见。含 DENV 抗原的细胞为 CD61(+)，似乎具有巨核细胞的特征。从 DENV 感染的 RM 中分离出的 CD61(+)细胞的动力学特征显示，在 DENV 感染后早期 CD61(+)CD62P(+)细胞短暂增加。在感染 RM 的高度富集的 CD61(+)细胞中观察到急性阶段的 DENV RNA。我们的结果表明，含有 CD61(+)细胞的病毒可能与登革热患者的血小板功能障碍和血小板计数低特征直接相关。
