Genetic basis of WNV vector competence in Culex tarsalis

描述（由申请人提供）：了解媒介种群的遗传学如何影响虫媒病毒的传播，对于了解疾病发病率的动态、开发新病毒引入的风险评估策略以及开发可用于有效靶向控制工作的病毒传播生物标志物至关重要。自1999年引入以来，西尼罗河病毒（WNV）已在美国本土完全传播，已造成23,000多例确诊人间病例，其中近900人死亡。最有效的实验室媒介已被证明是库蚊，它已被确定为美国西部非常重要的媒介。先前的研究和我们的初步数据已经证明了Cx具有显著的遗传结构。蚁群与Cx能力的地理差异。跗猴经口和垂直传播西尼罗河病毒。我们假设与媒介能力相关的遗传变异是造成西尼罗河病毒在中国传播的时空变异的部分原因。tarsalis。我们用Cx。tarsalis/WNV关系作为模型系统来研究蚊子种群的遗传如何控制引入的虫媒病毒在自然种群中的成功入侵和维持。我们已经开发了多种用于Cx的遗传标记系统。tarsalis。我们的具体目的是：1)对Cx进行群体遗传分析。利用线粒体序列数据和我们新开发的微卫星标记，鉴定与西尼罗河病毒载体能力相关的数量性状位点（QTL）。3)确定自然Cx中解释西尼罗河病毒载体能力的QTL。tarsalis人群。我们的结果将指导未来识别和验证Cx中负责西尼罗河病毒易感性的特定候选基因。确定特定基因在维持西尼罗河病毒在自然Cx中的传播中的作用。了解自然病媒种群的遗传如何制约引进的外来病原体的成功引进和维持。我们的工作将最终导致鉴定西尼罗河病毒传播的蚊子遗传生物标志物，可用于风险评估和有效靶向病媒控制工作。这项工作也与生物恐怖主义问题有重要的相关性，因为它将为蚊子种群中的内在媒介遗传因素如何影响释放的B类药剂的流行病学提供见解。

DESCRIPTION (provided by applicant): Knowledge of how the genetics of vector populations condition the spread of arboviruses is critical for understanding dynamics of disease incidence, development of risk assessment strategies for novel virus introductions and development of virus transmission biomarkers that can be used to efficiently target control efforts. Since its introduction in 1999, West Nile Virus (WNV) has spread completely across the contiguous United States and has been responsible for over 23,000 confirmed human cases with almost 900 deaths. The most efficient laboratory vector has been demonstrated to be Culex tarsalis, which has been identified as a very important vector in the western United States. Prior studies and our preliminary data have demonstrated significant genetic structure among Cx. tarsalis populations and geographic variation in the ability of Cx. tarsalis to transmit WNV orally and vertically. We hypothesize that genetic variation related to vector competence is partly responsible for temporal and spatial variation seen in WNV transmission in Cx. tarsalis. We will use the Cx. tarsalis/WNV relationship as a model system to investigate how the genetics of mosquito populations govern the successful invasion and maintenance of an introduced arbovirus in natural populations. We have developed multiple genetic marker systems for use in Cx. tarsalis. Our specific aims are to: 1) Conduct population genetic analysis of Cx. tarsalis populations using mitochondrial sequence data and our newly-developed microsatellite markers, 2) Identify quantitative trait loci (QTL) responsible for WNV vector competence in Cx. tarsalis using an Advanced Intercross Design and 3) Identify QTL explaining WNV vector competence in natural Cx. tarsalis populations. Our results will guide future efforts to identify and validate specific candidate genes responsible for WNV susceptibility in Cx. tarsalis, determine the role of specific genes in maintaining WNV transmission in natural Cx. tarsalis populations and understand how the genetics of natural vector populations condition the successful introduction and maintenance of introduced exotic pathogens. Our work will ultimately lead to the identification of mosquito genetic biomarkers for WNV transmission that can be used for risk assessment and effective targeting of vector control efforts. This work also has important relevance for bioterrorism issues because it will provide insight into how intrinsic vector genetic factors in mosquito populations affect the epidemiology of a released Category B agent.