Tadkalkar Nitali, Prasad Sharda, Gangodkar Shobha, Ghosh Kanjaksha, Basu Atanu
Electron Microscopy and Pathology Group, National Institute of Virology, 20A, Dr. Ambedkar Road, Pune, 411001 India.
Indian J Hematol Blood Transfus. 2019 Jul;35(3):502-506. doi: 10.1007/s12288-018-1058-2. Epub 2018 Dec 6.
Hematological abnormalities and altered vascular permeability are frequently encountered in Dengue virus infected patients, but the mechanisms that alter platelet-endothelium interactions remain incompletely understood. The DENV NS1 protein has been implicated in adverse disease outcomes. In the present study the role of NS1 protein in affecting the expression of vWF and platelet adhesion properties of endothelial cells was studied in vitro. The results suggest that vWF is down regulated in cultured endothelial cells 6 and 24 h after exposure with increase in vWF levels in culture supernatants at corresponding time points. Ultrastructural studies showed distinct evidence of endothelial cell activation morphology and degranulation of Weibel-Palade bodies in NS1 exposed cells that also showed increased platelet activation physiology. The findings suggest that changes in vWF production and secretion may be induced in endothelial cells exposed to DENV NS1 protein; and play a role in bleeding complications of severe DENV disease.
登革热病毒感染患者常出现血液学异常和血管通透性改变,但改变血小板与内皮细胞相互作用的机制仍未完全明确。登革热病毒非结构蛋白1(DENV NS1)与不良疾病转归有关。在本研究中,我们在体外研究了NS1蛋白对血管性血友病因子(vWF)表达及内皮细胞血小板黏附特性的影响。结果表明,培养的内皮细胞在暴露于NS1后6小时和24小时,vWF表达下调,而相应时间点培养上清液中的vWF水平升高。超微结构研究显示,暴露于NS1的细胞有明显的内皮细胞激活形态学证据以及Weibel-Palade小体脱颗粒,同时血小板激活生理学也增强。这些发现提示,暴露于DENV NS1蛋白的内皮细胞中vWF的产生和分泌可能发生改变,并在严重登革热疾病的出血并发症中起作用。