Molecular Genetics of Dengue Resistance in Mosquitoes

蚊子抗登革热的分子遗传学

• 批准号: 6899798
• 负责人: DAVID W SEVERSON
• 金额: $ 62.89万
• 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/6899798
• 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; 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）：在大多数热带国家，节肢动物传播的病毒疾病已重新成为主要健康问题。在PAT 20年中，登革热的发病率大大增加，包括其出血形式与相关的人死亡。登革热是对25亿人口的一种享受，估计每年的发病率为500-1亿，每年约有24,000例DHF。登革热控制工作受到疫苗开发的缺乏，蚊子载体中杀虫剂耐药性的发展以及有组织的蚊子控制工作的总体下降而受到限制。该提案的目的是识别，隔离和表征与登革热病毒的蚊子向量能力相关的遗传因素，其长期目标是使用此信息来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。所提出的目标是基于以下一般假设：在实验室菌株和蚊子埃德斯埃及埃及的实验室菌株和地理田间集合中，可以鉴定出对不同登革热血清型受到差异调节的核心基因套件。该研究计划采用了AE的第一批产品之一。 Aegypti基因组项目，微孔阵列和部分测序的cDNA，是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AE中进行高通量表达分析的应用。在登革热病毒挑战之后的埃及，对差异表达基因的详细分析以及从实验室研究中获得的信息快速过渡到现场研究。现场研究将在特立尼达和海地进行，因为它们分别代表了有组织的登革热国家与有限的载体控制计划。该项目的具体目的是：1）表征AE中的差异基因表达模式。埃及登革热血液粉； 2）进行功能分析OD候选登革热载体能力基因； 3）研究选定的生物和非生物因子对地方性地区登革热传播的影响，包括通过微阵列分析鉴定的关键候选登革热媒介能力基因。