Dengue virus-induced hemorrhage in a nonhuman primate model
Dengue virus-induced hemorrhage in a nonhuman primate model
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DOI：
10.1182/blood-2009-09-242990
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发表时间：
2010-03-04
期刊：
影响因子：
20.3
通讯作者：
Perng, Guey Chuen
中科院分区：
文献类型：
--
作者：
Onlamoon, Nattawat;Noisakran, Sansanee;Perng, Guey Chuen
缺乏再现人登革病毒感染的登革出血性动物模型一直是推进我们对登革疾病发病机制所涉及的早期事件的理解的重大障碍。为了解决这一问题，一组恒河猴以1 x 10（7）PFU/动物的剂量静脉内感染登革热病毒血清2型（毒株16 681）。6只动物中的6只在感染后3至5天出现典型的登革热出血。血液化学似乎是正常的，除了肌酸磷酸激酶，在感染后7天达到峰值。记录了中度血小板减少症和明显的中性粒细胞减少症，伴血红蛋白和红细胞压积轻微降低。此外，D-二聚体浓度显著升高。病毒血症在感染后3 - 5天达到峰值，随后T和B淋巴细胞之间呈反比关系，血小板-单核细胞和血小板-中性粒细胞聚集体呈双峰模式。在感染后8或9天观察到含有单核细胞吞噬的血小板的登革病毒。因此，静脉注射高剂量登革病毒的恒河猴产生登革出血，这可能提供一个独特的平台来定义登革病毒感染的早期事件，并帮助确定哪些血液成分有助于登革疾病的发病机制。（血。2010;115：1823-1834）
Lack of a dengue hemorrhagic animal model recapitulating human dengue virus infection has been a significant impediment in advancing our understanding of the early events involved in the pathogenesis of dengue disease. In efforts to address this issue, a group of rhesus macaques were intravenously infected with dengue virus serotype 2 (strain 16 681) at 1 x 10(7) PFU/animal. A classic dengue hemorrhage developed 3 to 5 days after infection in 6 of 6 animals. Blood chemistry appeared to be normal with exception of creatine phosphokinase, which peaked at 7 days after infection. A modest thrombocytopenia and noticeable neutropenia concomitant with slight decrease of hemoglobin and hematocrit were registered. In addition, the concentration of D-dimer was elevated significantly. Viremia peaked at 3 to 5 days after infection followed by an inverse relationship between T and B lymphocytes and a bimodal pattern for platelet-monocytes and platelet-neutrophil aggregates. Dengue virus containing platelets engulfed by monocytes was noted at 8 or 9 days after infection. Thus, rhesus macaques inoculated intravenously with a high dose of dengue virus produced dengue hemorrhage, which may provide a unique platform to define the early events in dengue virus infection and help identify which blood components contribute to the pathogenesis of dengue disease. (Blood. 2010;115:1823-1834)