Mosquito-Virus-Host Interactions and WNV Pathogenesis

蚊子-病毒-宿主相互作用和西尼罗河病毒发病机制

• 批准号: 6912907
• 负责人: KRISTEN A BERNARD
• 金额: $ 25万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6912907
• 关键词: Culex; West Nile virus; arthropod borne communicable disease; chickens; disease vectors; green fluorescent proteins; host organism interaction; immune response; interferon alpha; interferon beta; laboratory mouse; songbirds; tissue /cell culture; virus cytopathogenic effect; virus load; virus replication

Description (provided by applicant): 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 of 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.

描述（由申请人提供）：节肢动物传播病毒（arbovirus）存在于其节肢动物载体和脊椎动物宿主之间的复杂周期中。西尼罗河病毒（WNV）是一种导致严重人类和兽医疾病的arbovirus，通过鸟类和库氏菌之间的循环来维持自然界。蚊子。动态蚊子脊椎动物宿主的相互作用不仅涉及Enzootic传播的效率，而且还参与疾病的发病机理。当前，蚊子传播对脊椎动物中WNV感染的影响很差。这项研究建议的目的是进一步了解WNV与其脊椎动物和无脊椎动物宿主的相互作用，以制定新颖的控制和治疗策略。基于初步数据，与针接种相比，蚊子感染WNV的鸡的早期病毒血症高100倍，中央假设是蚊子传播增强了其脊椎动物宿主中WNV感染的最早步骤。检验该假设的研究将使用以下方法：1）将比较复制的原发性和次要部位的病毒复制，以便在鸡和小鼠中自然蚊子传播和WNV的针头接种； 2）WNV的蚊子传播的不同方面将测试其对鸡的eady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）将确定负责早期病毒血症的机制，特别是对宿主I型干扰素反应的影响将在体内和体外检查。这项研究的完成将进一步阐明WNV与蚊子与放大（鸟）和附带（小鼠）宿主的相互作用，并将定义蚊子唾液在WNV传播和疾病中起的关键作用。本应用中提出的研究很重要，因为了解这种复杂的相互作用对于制定WNV的创新治疗和控制策略至关重要。