Molecular Genetics of Dengue Resistance in Mosquitoes

蚊子抗登革热的分子遗传学

• 批准号: 7070021
• 负责人: DAVID W SEVERSON
• 金额: $ 63.24万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7070021
• 关键词: Aedes; Caribbean islands; arthropod borne communicable disease; arthropod genetics; complementary DNA; dengue virus; disease vectors; field study; gene expression; genetic regulation; genetic strain; guinea pigs; laboratory mouse; laboratory rat; life cycle; microarray technology; molecular genetics; polymerase chain reaction; serotyping

DESCRIPTION (provided by the applicant): Arthropod-borne viral disease have re-remerged as major health problems in most tropical countries. The incidence of dengue fever has increased greatly over the pat 20 years, including its hemorrhagic form with associated human fatalities. Dengue is a treat to >2.5 billion people, with a annual incidence estimated at 50-100 million and several hundred thousand cases of DHF with approximately 24,000 death per year. Dengue control efforts have been limited by the lack of progress in vaccine development, development of insecticide resistance in mosquito vectors, and the general decline in organized mosquito control efforts. The objective of this proposal is to identify, isolate and characterize genetic factors associated with mosquito vector competence for dengue virus, with a long-term goal of using this information to develop novel dengue disease control strategies aimed toward disrupting the pathogen life cycle. The proposed objectives are based on the general hypothesis that a core suite of genes that are differentially regulated in response to exposure to different dengue serotypes can be identified among both laboratory strains and geographic field collections of the mosquito, Aedes aegypti. The research plan employs one of the first products of the Ae. aegypti genome project, microplate-arrayed and partially sequenced cDNAs, as a gateway into the eventual complete elucidation of these gene relationships and their phenotypic outcome. The outlined experiments represent the application of first generation cDNA micro-arrays for high-throughput expression analysis in Ae. aegypti following a dengue virus challenge, detailed analysis of differentially expressed genes, and the rapid transition of information gained from laboratory studies into field studies. Field studies will be conducted in Trinidad and Haiti, as they represent dengue endemic countries with organized versus limited vector control programs, respectively. The specific aims of this project are: 1) characterize differential gene expression patterns in Ae. aegypti following a dengue-infected blood meal; 2) conduct functional analysis od candidate dengue vector competence genes; and, 3) investigate the impact of selected biotic and abiotic factors on dengue transmission in endemic areas, including key candidate dengue vector competence genes identified by micro-array analysis.

描述（由申请人提供）：节肢动物传播的病毒性疾病已重新成为大多数热带国家的主要健康问题。过去 20 年来，登革热的发病率大幅增加，其中包括导致人类死亡的出血性登革热。登革热是超过 25 亿人的疾病，每年发病人数估计为 50-1 亿，登革热病例有数十万例，每年约有 24,000 人死亡。由于疫苗开发缺乏进展、蚊媒对杀虫剂产生抗药性以及有组织的蚊子控制工作普遍下降，登革热控制工作受到限制。该提案的目的是识别、分离和表征与登革热病毒蚊媒能力相关的遗传因素，长期目标是利用这些信息开发旨在破坏病原体生命周期的新型登革热疾病控制策略。所提出的目标基于这样的一般假设：可以在埃及伊蚊的实验室菌株和地理现场收集中鉴定出一组核心基因，这些基因因暴露于不同登革热血清型而受到差异性调节。该研究计划采用了 Ae 的首批产品之一。埃及伊蚊基因组计划、微孔板阵列和部分测序的 cDNA，作为最终完全阐明这些基因关系及其表型结果的门户。概述的实验代表了第一代 cDNA 微阵列在伊蚊高通量表达分析中的应用。埃及伊蚊在登革热病毒攻击后，对差异表达基因进行详细分析，并将从实验室研究获得的信息快速转变为实地研究。实地研究将在特立尼达和海地进行，因为这两个国家分别代表着有组织的和有限的病媒控制计划的登革热流行国家。该项目的具体目标是：1）表征AE的差异基因表达模式。感染登革热的血液后感染埃及伊蚊； 2) 对候选登革热载体能力基因进行功能分析； 3) 研究选定的生物和非生物因素对流行地区登革热传播的影响，包括通过微阵列分析确定的关键候选登革热媒介能力基因。