HANTAVIRUS INFECTIONS--ECOLOGY, IMMUNITY AND TREATMENT

这项计划的最终目的是降低高死亡率 鼠媒人兽共患病(HPS和玻利维亚出血热) 美洲。我们的跨学科团队将结合 预测有利于人畜共患病爆发的环境事件， 具有早期诊断和靶向治疗的能力 对免疫发病和抗病毒治疗有扎实的知识。 第一个项目将开发预测SNV突发的能力 利用对啮齿动物的纵向研究，研究啮齿动物种群的感染情况 丰度、密度和感染率，再加上实验结果- 人工操纵啮齿动物密度的人工建造的地块。它 将检验这样一种假设，即某些栖息地提供了 持续的啮齿动物感染，邻近的栖息地感染 当气候条件有利于增加啮齿动物密度和 感染。基于地理信息系统的数据(核心A)将转化为 将鼠密度和SNV流行率纳入大尺度标志物进行预测 增加了人类感染的风险。项目将扩大这些生态系统 玻利维亚鼠类感染马丘波病毒的研究，并将检测 玻利维亚出血热暴发仅限于 整个范围的一小部分，因为，像 汉坦病毒，选定的栖息地有利于持续的啮齿动物感染 在环境和人类干扰后蔓延到人类宿主。 第三个项目检测表位特异性和细胞因子的分泌。 急性HPS患者的T细胞克隆和T细胞模式及其检测 假设大量毛细血管渗漏是由于T细胞过多所致 刺激。它将产生另一种疗法来终止细胞因子 风暴和降低死亡率。

The ultimate aim of this program is to decrease the high mortality of rodent-borne viral zoonoses (HPS and Bolivian hemorrhagic fever) in the Americas. Our interdisciplinary team will combine the capability of predicting environmental events that favor outbreaks of zoonotic disease, with the capability of early diagnosis and targeted therapy based on a sound knowledge of immumnopathogenesis and antiviral therapy. The first Project will develop a capability to predict bursts of SNV infection in rodent populations, using longitudinal studies of rodent abundance, density and infection rate, coupled with experimentally- constructed plots in which rodent density is artificially manipulated. It will test the hypothesis that certain habitats provide a nidus of persistent rodent infection, from which adjacent habitats are infected by spillover when climatic conditions favor increase rodent density and infection. GIS-based data (Core A) will translate small-scale measures of rodent density and SNV prevalence into large-scale markers to predict increased risk of human infection. Project will extend these ecologic studies to Machupo virus infection of rodents in Bolivia, and will test the hypothesis that Bolivian hemorrhagic fever outbreaks are restricted to a fraction of the entire range of Calomys callosus host, because, like hantaviruses, selected habitats favor persistent rodent infection that spills over into human hosts after environmental and human disturbances. The third project examines the epitope specificity and cytokine secretion patterns of T cell clones and T cells from acute HPS patients and will test the hypothesis that the massive capillary leak is due to excessive T cell stimulation. It will yield alternative therapies to abort the cytokine storm and reduce mortality.