Mosquito-Virus-Host Interactions and WNV Pathogenesis

节肢动物传播的病毒（虫媒病毒）存在于它们的节肢动物载体和 脊椎动物宿主西尼罗河病毒（WNV）是一种引起重大人类和兽医疾病的虫媒病毒， 在自然界中通过鸟类和库蚊之间的循环来维持。蚊子动态蚊子病毒- 脊椎动物与宿主的相互作用不仅与地方病传播的效率有关， 疾病的发病机制。目前，蚊子传播对脊椎动物中WNV感染的影响 定义不明确。本研究的目的是进一步了解 西尼罗河病毒与其脊椎动物和无脊椎动物宿主，以开发新的控制和治疗策略。 根据初步数据，蚊子感染西尼罗河病毒的鸡的早期病毒血症高出100倍， 与针接种相比，中心假设是蚊子传播增强了最早的 WNV感染脊椎动物宿主的步骤。检验这一假设的研究将使用以下方法 方法：1）病毒复制的主要和次要网站o [复制将比较自然 西尼罗河病毒在鸡和小鼠中的蚊虫传播和针接种; 2）蚊子的不同方面 西尼罗河病毒的传播将测试它们对鸡的早期病毒血症的影响，包括病毒剂量，唾液， 蚊子探测和蚊子衍生的病毒; 3）负责早期病毒血症的机制将是 将在体内和体内检测对宿主I型干扰素应答的影响， 体外这项研究的完成将进一步阐明西尼罗河病毒和蚊子的相互作用， （鸟）和偶然（小鼠）宿主，并将确定蚊子唾液在西尼罗河病毒中发挥的关键作用 传播和疾病。本申请中提出的研究是重要的，因为了解这一点， 复杂的相互作用对于开发西尼罗河病毒的创新治疗和控制策略至关重要。

Arthropod-borne viruses (arboviruses) exist in a complex cycle between their arthropod vector and vertebrate host. West Nile virus (WNV), an arbovirus that causes significant human and veterinary disease, is maintained in nature by cycling between birds and Culex spp. mosquitoes. The dynamic mosquito-virus- vertebrate host interaction is involved not only in the efficiency of enzootic transmission, but also in the pathogenesis of disease. Currently, the impact of mosquito transmission on WNV infection in the vertebrate is poorly defined. The objective of this research proposal is to further our understanding of the interaction of WNV with its vertebrate and invertebrate hosts in order to develop novel control and treatment strategies. Based on preliminary data that early viremia is 100-fold higher in chickens infected with WNV by mosquitoes compared to needle inoculation, the central hypothesis is that mosquito transmission enhances the earliest steps of WNV infection in its vertebrate host. Studies to test this hypothesis will use the following approaches: 1) viral replication in primary and secondary sites o[ replication will be compared for natural mosquito transmission and needle inoculation of WNV in chickens and mice; 2) different aspects of mosquito transmission of WNV will be tested for their effect on eady viremia in chickens, including viral dose, saliva, mosquito probing and mosquito-derived virus; 3) the mechanism responsible for the early viremia will be identified, and in particular the effect on the host's Type I interferon response will be examined in vivo and in vitro. Completion of this study will further elucidate the interaction of WNV and the mosquito with amplifying (bird) and incidental (mouse) hosts and will define the critical role that mosquito saliva plays in WNV transmission and disease.The research proposed in this application is significant because understanding this complex interaction is essential to developing innovative treatment and control strategies for WNV.