EPIDEMIC POTENTIAL OF EMERGING REASSORTANT BUNYAVIRUSES

这项研究的长期目标是确定流行潜力 加州血清群（CAL）本扬病毒进化事件的研究。 CAL病毒中枢神经系统（CNS）感染数量空前 最近在俄罗斯被诊断出来，而耐药的CAL病毒已经 被孤立。这些CNS感染的发病率增加是否 新出现的布尼亚病毒，布尼亚病毒进化 事件，向量相关的现象，或其他因素将是 研究了因为医学上重要的CAL病毒及其 矢量是全北极分布，我们的研究将提供关键 关于CAL病毒演变的流行病学后果的信息， 北美以及俄罗斯。 来自俄罗斯和北美的CAL病毒的进化潜力 将在自然和替代媒介物种中确定。的能力 将确定选择的CAL病毒以重新分类它们的RNA片段。 载体和病毒系统发育对重配潜力的限制将 被确定。分子内进化将通过直接的 从受感染蚊子中扩增病毒序列;聚合酶 将使用链式反应（PCR）扩增靶病毒基因组 序列从蚊子，变性梯度凝胶电泳用于 用于测序的同一性候选物，以及用于定义 隔离物之间的差异。 这些研究将提供信息 关于虫媒病毒循环在促进病毒基因组 稳定性或可塑性以及载体通道在维持 虫媒病毒循环完整性和传播潜力。特定分子 探针、PCR方案和免疫学技术将被开发用于 CAL病毒的快速基因型鉴定和诊断。许多 与CAL病毒的全北极传播相关的媒介物种是 物种复杂的成员，难以通过常规方法识别 分类标准分子技术将发展到识别 特别是与病毒传播有关的媒介物种。 病毒基因型、媒介物种和疾病之间的关系 俄罗斯的情况也将得到说明。CAL病毒以前 分离的或新分离的载体，以及来自人类中枢神经系统 发生的感染将是基因型、表型和 生物学特征，后者在载体和脊椎动物方面 主机交互。 这些研究将提供关于 CAL病毒的分布和病毒基因型之间的关系， 病媒物种和中枢神经系统疾病发病率。这样的知识， 对于最终发展有效的监测、诊断 以及对这些人类重要病原体的控制策略。

The long-term goal of this research is to determine the epidemic potential of California serogroup (CAL) bunyavirus evolutionary events. Unprecedented numbers of CAL virus central nervous system (CNS) infections recently have been diagnosed in Russia, and reassortant CAL viruses have been isolated. Whether the increased incidence of these CNS infections is attributable to newly emerged bunyaviruses, to bunyavirus evolutionary events, to vector-associated phenomena, or to other factors will be investigated. Because the medically-important CAL viruses and their vectors are holarctic in distribution, our studies will provide critical information about the epidemiologic consequences of CAL virus evolution in North America as well as in Russia. The evolutionary potential of CAL viruses from Russia and North America will be determined in natural and alternate vector species. The ability of selected CAL viruses to reassort their RNA segments will be determined. Vector and viral phylogenetic constraints on reassortment potential will be determined. Intramolecular evolution will be investigated by direct amplification of virus sequences from infected mosquitoes; polymerase chain reaction (PCR) will be used to amplify target viral genomic sequences from mosquitoes, denaturing gradient gel electrophoresis used to identity candidates for sequencing, and sequence analyses used to define differences between isolates. These studies will provide information concerning the role of the arbovirus cycle in promoting viral genomic stability or plasticity and the role of vector passage in maintaining arbovirus cycle integrity and transmission potential. Specific molecular probes, PCR protocols, and immunologic techniques will be developed for rapid genotypic identification and diagnosis of CAL viruses. Many of the vector species associated with holarctic transmission of CAL viruses are members of species complexes and difficult to identity by conventional taxonomic criteria. Molecular techniques will be developed to identity specifically the vector species involved in virus transmission. Relationships between viral genotypes, vector species, and disease incidence in Russia will also be elucidated. CAL viruses previously isolated or newly isolated and vectors from premises where human CNS infections have occurred will be genotypically, phenotypically, and biologically characterized, the latter in terms of vector and vertebrate host interactions. These studies will provide information on the distribution of CAL viruses and relationships between viral genotypes, vector species, and CNS disease incidence. Such knowledge will be essential for eventual development of effective surveillance, diagnosis, and control strategies for these important pathogens of humans.