EPIDEMIC POTENTIAL OF EMERGING REASSORTANT BUNYAVIRUSES

这项研究的长期目标是确定流行的可能性 加州血清组(CAL)本亚病毒进化事件。 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，重新组合的CAL病毒 被隔离了。这些中枢神经系统感染增加的发病率是否 归因于新出现的本雅病毒，归因于本雅病毒的进化 事件、与矢量相关的现象或其他因素 调查过了。因为具有重要医学意义的CAL病毒及其 媒介在全北极的分布，我们的研究将提供关键的 关于CAL病毒演变的流行病学后果的信息 北美和俄罗斯也是。 俄罗斯和北美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 将确定选定的CAL病毒对其RNA片段进行重新配对。 载体和病毒系统发育对重组潜力的限制将 要下定决心。分子内进化将由直接的 从受感染的蚊子中扩增病毒序列；聚合酶 链式反应(PCR)将被用于扩增靶病毒基因组 蚊子的序列，变性梯度凝胶电泳法用于 用于测序的候选身份，以及用于确定 不同菌株之间的差异。这些研究将提供信息 关于虫媒病毒周期在促进病毒基因组方面的作用 稳定性或可塑性与载体通道在维持中的作用 虫媒病毒循环的完整性和传播潜力。特定分子 将开发探针、聚合酶链式反应方案和免疫学技术 CAL病毒的快速基因分型和诊断。许多人 与CAL病毒在全北极传播有关的媒介物种有 物种复合体的成员，很难通过常规方式进行识别 分类标准。分子技术将被发展到身份识别 具体地说，涉及病毒传播的媒介物种。 病毒基因型别、病媒种类与疾病的关系 俄罗斯的发病率也将被阐明。以前的卡尔病毒 从人类CNS所在的场所分离或新分离的媒介 已发生的感染将是遗传型的、表型的和 生物学特征，后者在媒介和脊椎动物方面 主持人互动。这些研究将提供有关 CAL病毒的分布和病毒基因型间的关系， 媒介种类和中枢神经系统疾病发病率。这样的知识将是 对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.