Host-targeted Interventions of Category A, B and C Bunyaviruses

我们的项目集中在医学上重要的A、B和C类本扬病毒，这些病毒引起出血性 人类的发热、心肺表现和脑炎。大多数布尼亚病毒是虫媒病毒， 自然界中涉及温血脊椎动物物种和节肢动物载体复制的生命周期。物种 这项提议的核心包括克里米亚刚果出血热病毒（CCHFV）、裂谷热病毒 （RVFV）、Sin Nombre病毒（SNV）和长曲棍球病毒（LACV）。这些病毒是新出现的人畜共患病 由于不断变化的地理和环境相互作用， 人类和自然界中的宿主。我们的项目是基于初步数据表明， 布尼亚病毒复制与细胞质mRNA降解和相关RNA 控制复制过程中的路径。我们使用微阵列数据来定义一组细胞基因， 在感染CCHFV、RVFV和SNV后类似地上调或下调的控制途径。的 该项目围绕两个具体目标开展。目的1是从我们的限制性内切酶中鉴定细胞靶基因， 布尼亚病毒复制所需的一组候选宿主因子的开始。这些细胞因子将 是治疗干预的高潜力的有吸引力的候选者。目的2：检验假设， 布尼亚病毒复制所需的那些基因对于有效的病毒转录或基因组是必需的 复制的

Our project focuses on medically important Category A, B, and C bunyaviruses that cause hemorrhagic fever, cardiopulmonary manifestations, and encephalitis in humans. Most bunyaviruses are arboviruses with a life cycle involving replication in warm-blooded vertebrate species and arthropod vectors in nature. Species central to this proposal include Crimean Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), Sin Nombre virus (SNV), and LaCrosse virus (LACV). These viruses epitomize emerging zoonotic viruses that threaten human populations due to changing geographic and environmental interactions among human and natural reservoirs harboring these viruses. Our project is based on preliminary data indicating that bunyavirus replication physically engages with the cytoplasmic mRNA degradation and related RNA control pathways during replication. We used microarray data to define a set of cellular genes from these control pathways that are similarly up- or down-regulated following infection CCHFV, RVFV, and SNV. The project is organized around two specific aims. Aim 1 is to identify cellular target gene(s) from our restricted starting set of candidate host factors that are required for bunyavirus replication. Such cellular factors would be attractive candidates of high potential for therapeutic intervention. Aim 2 with test the hypothesis that those genes required for bunyavirus replication are necessary for efficient viral transcription or genome replication.