HANTAVIRUS INFECTIONS--ECOLOGY, IMMUNITY AND TREATMENT

该计划的最终目的是降低高死亡率， 啮齿动物传播的病毒性人畜共患病（HPS和玻利维亚出血热） 美洲. 我们的跨学科团队将结合联合收割机的能力， 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， 对免疫发病机制和抗病毒治疗有较好认识。 第一个项目将开发预测SNV爆发的能力 啮齿类动物感染，采用啮齿类动物纵向研究 丰度，密度和感染率，再加上实验- 人工控制啮齿类动物密度的试验区。 它 将检验这样一个假设，即某些栖息地提供了一个 持续的啮齿动物感染，邻近的栖息地受到感染， 当气候条件有利于增加啮齿动物密度时， 感染 基于地理信息系统的数据（核心A）将转化为小规模的 啮齿动物密度和SNV流行率成大尺度指标进行预测 增加人类感染的风险。 该项目将扩大这些生态 在玻利维亚研究马丘波病毒感染啮齿动物，并将测试 玻利维亚出血热暴发仅限于 小家鼠宿主的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会溢出到人类宿主体内。 第三个项目检查表位特异性和细胞因子分泌 急性HPS患者的T细胞克隆和T细胞的模式，并将测试 假设大量毛细血管渗漏是由于过量的T细胞 刺激. 它将产生替代疗法来中止细胞因子 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.