Apoptosis as an anti-viral response in mosquito midgut

细胞凋亡作为蚊子中肠的抗病毒反应

基本信息

批准号：
7229870
负责人：
ROLLIE J CLEM
金额：
$ 21.26万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7229870
关键词：
Address Aedes Alphavirus Anopheles gambiae Antiviral Response Apoptosis Apoptotic Arboviruses Attention Baculoviruses Biology Blood Caspase Inhibitor Cells Chemicals Collection Communicable Diseases Complex Culicidae Data Dengue Dengue Hemorrhagic Fever Dengue Virus Engineering Environmental Risk Factor Epithelial Cells Epithelium Explosion Fibrinogen Genes Genetic Genomics Goals Green Fluorescent Proteins Immune Immune response Immune system Immunofluorescence Immunologic Infection Insect Vectors Insecta Knowledge La Crosse virus Laboratories Lead Literature Microscopic Midgut Molecular Numbers Organ Pathway interactions Personal Satisfaction Phagocytosis Play Population RNA Interference Recombinants Refractory Regulator Genes Reporting Research Personnel Role Salivary Glands TdT-Mediated dUTP Nick End Labeling Assay Techniques Technology Testing Thinking Time Tissues Viral Viral Encephalitis Virus Virus Diseases Virus Replication West Nile Fever West Nile virus Western Equine Encephalitis Virus Yellow Fever Yellow fever virus arbovirus disease base disease transmission feeding improved programs transmission process vector vector mosquito

项目摘要

DESCRIPTION (provided by applicant): Mosquitoes are important vectors for a number of infectious diseases caused by arboviruses including West Nile virus, dengue virus, yellow fever virus, LaCrosse virus, and Venezuelan, eastern and western equine encephalitis viruses. Mosquitoes acquire arboviruses from vertebrate hosts during blood feeding, and after entry into the mosquito vector, the virus must first infect, replicate in, and escape from the epithelial cells of the midgut before it can be disseminated to other organs. Dissemination to the salivary glands is necessary for transmission to another host. Thus, the midgut epithelium constitutes a potential barrier to infection and subsequent transmission, and is therefore a target for interrupting the transmission cycle. It is well documented that only certain vector-virus combinations result in efficient transmission of disease, and data exist indicating that arboviruses must overcome the immune defenses of the insect vector in order to be transmitted successfully. However, little is known about anti-viral defenses in insects. For several years the Clem laboratory has been studying the role of apoptosis in defense against baculovirus infection in lepidopteran insects. This application seeks to explore the question of whether apoptosis can serve as a defense against arbovirus invasion in the mosquito midgut. In order to accomplish this goal a strong and diverse team has been assembled that includes expertise in apoptosis, mosquito vector biology, and arboviruses. In Aim 1, midguts and other tissues from arbovirus-infected mosquitoes will be examined for apoptosis, including a collection of Aedes aegypti strains that vary in their ability to vector dengue virus. In Aim 2, the hypothesis that apoptosis can limit virus replication and spread will be directly tested by manipulating apoptotic pathways in the mosquito and examining the effects on the ability of arboviruses to successfully cause disseminated infections.

描述（申请人提供）：蚊子是由虫媒病毒引起的多种传染病的重要媒介，包括西尼罗河病毒、登革热病毒、黄热病病毒、曲棍球病毒以及委内瑞拉、东西方马脑炎病毒。蚊子在吸血过程中从脊椎动物宿主获得虫媒病毒，进入蚊媒后，病毒必须首先感染、复制并从中肠上皮细胞中逃逸，然后才能传播到其他器官。传播到唾液腺对于传播到另一个宿主是必要的。因此，中肠上皮构成了感染和随后传播的潜在屏障，因此是中断传播周期的目标。有充分证据表明，只有某些载体-病毒组合才能有效传播疾病，并且有数据表明虫媒病毒必须克服昆虫载体的免疫防御才能成功传播。然而，人们对昆虫的抗病毒防御知之甚少。多年来，克莱姆实验室一直在研究细胞凋亡在鳞翅目昆虫防御杆状病毒感染中的作用。本申请旨在探讨细胞凋亡是否可以作为蚊子中肠中虫媒病毒入侵的防御措施。为了实现这一目标，我们组建了一支强大而多元化的团队，其中包括细胞凋亡、蚊媒生物学和虫媒病毒方面的专业知识。在目标 1 中，将检查虫媒病毒感染蚊子的中肠和其他组织的细胞凋亡情况，其中包括传播登革热病毒能力各异的埃及伊蚊菌株集合。在目标 2 中，细胞凋亡可以限制病毒复制和传播的假设将通过操纵蚊子中的细胞凋亡途径并检查对虫媒病毒成功引起播散性感染的能力的影响来直接测试。