BUNYAVIRUS/MOSQUITO INTERACTIONS

描述（改编自申请人的摘要）：本发明的总体目标是： 研究的目的是检查最初的分子相互作用， 确定布尼亚病毒感染蚊子能力的第一步 vector.布尼亚病毒是人类疾病的重要原因， 世界各地的家畜大多数布尼亚病毒传播给人类， 动物蚊子他们将使用拉克罗斯脑炎病毒（LACV）， 其自然蚊子媒介三列伊蚊用于这些研究。他们将 研究病毒糖蛋白在病毒与蚊子结合中的作用 中肠，在感染Ae.三列的LACV，并在特异性 选定蚊子物种的LACV。它们将完全产生传染性LACV 使用基于RNA聚合酶1的系统， 逆转流感病毒。它们会引入特定的突变 以及嵌合片段和基因到LACV中。基于大量的工作 在他们的实验室中，他们假设拉克罗斯的G2包膜蛋白 病毒对于病毒与蚊子中肠细胞的结合至关重要， 因此对蚊子感染至关重要。他们将确定蛋白质序列 的G2，这是需要的结合拉克罗斯病毒的中肠细胞， 它的自然蚊子媒介，以及另一种允许的蚊子物种。他们 将确定载体特异性是否部分由肽介导 病毒糖蛋白中的序列，如果这些序列相同， 测定病毒与感受态载体蚊子中肠细胞的结合。的 开发有效的技术来产生含有 特异性突变将允许在体内研究单个基因 在蚊子感染和哺乳动物发病机制中的作用

DESCRIPTION (Adapted from the Applicant's Abstract): The overall goal of this research is to examine the initial molecular interactions that are a critical first step in determining the ability of a bunyavirus to infect ist mosquito vector. Bunyaviruses are a significant cause of disease in humans and in domestic animals worldwide. Most bunyaviruses are transmitted to humans and animals by mosquitoes. They will use La Crosse encephalitis virus (LACV) and its natural mosquito vector Aedes triseriatus for these studies. They will examine the role viral glycoproteins play in the binding of virus to mosquito midgut, in the infection of Ae. triseriatus by LACV, and in the specificity of LACV for selected mosquito species. They will generate infectious LACV entirely from cloned cDNA using a RNA polymerase 1-based system that was recently used to reverse engineer influenza viruses. They will introduce specific mutatuions and chimeric segments and genes into LACV. Based on a significant body of work in their laboratory, they hypothesize that the G2 envelope protein of La Crosse virus is critical for virus binding to the cells of the mosquito midgut, and thus critical for mosquito infection. They will determine the protein sequences of G2 that are required for biding of La Crosse virus to the midgut cells of its natural mosquito vector, and to another permissive mosquito species. They will determine if vector specificity, in part, is mediated by pepetide sequences in the viral glycoproteins and if these sequences are the same that determine virus binding to midgut cells of competent vector mosquitoes. The development of efficient techniques to generate bunyaviruses containing specific mutations will permit in vivo investigations of individual gene functions in mosquito infections and in mammalian pathogenesis