Yellow Fever/Dengue Virus Competence in Aedes aegypt aegypti/formosus in Senegal

塞内加尔埃及伊蚊/台湾伊蚊的黄热病/登革热病毒能力

• 批准号: 7696878
• 负责人: WILLIAM C. BLACK
• 金额: $ 35.78万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7696878
• 关键词: Abdomen; Address; Adult; Aedes; Africa; Africa South of the Sahara; African; Agreement; Area; Asians; Behavior; Burkina Faso; Caribbean region; Characteristics; Chest; Chromosome Mapping; Chromosome inversion; Chromosomes; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 3; Collection; Competence; Complementary DNA; Culicidae; Data; Dengue; Dengue Virus; Disease; Funding; Gambia; Genes; Genetic; Genetic Markers; Genetic Recombination; Genetic Vectors; Genome; Genome Mappings; Geographic Distribution; Geographic Locations; Ghana; Goals; Habitats; Human; Hybrids; Individual; Infection; Island; Isoenzymes; Jamaica; Knowledge; Licensing; Light; Literature; Location; Maps; Measures; Midgut; Mitochondria; Mitochondrial DNA; Mosquito Control; Nuclear; Paracentric Inversion; Parents; Pattern; Penetration; Poaceae; Population; Population Dynamics; Population Genetics; Predisposition; Prevalence; Publications; Publishing; Quantitative Trait Loci; Relative (related person); Research; Saints; Senegal; Serotyping; Single Nucleotide Polymorphism; Site; Solid; South America; Surveys; Testing; Time; Vaccines; Virus; Visit; Work; Yellow Fever; Yellow Fever Virus Infection; Yellow fever virus; base; conditioning; disorder control; egg; falls; forest; insight; offspring; public health relevance; research study; trait; vector; vector control

DESCRIPTION (provided by applicant): Aedes aegypti sensu latu (s.l.) is the primary vector to humans of yellow fever virus (YFV) and the four serotypes of dengue virus (DENV1-4). Without a licensed vaccine for DENV, and despite the existence of a safe, effective YFV vaccine, control of these diseases still primarily relies on vector control. Our long term goal is to increase knowledge of local population dynamics to generate more focused, appropriate, and hopefully sustainable control strategies. There are two recognized subspecies of Ae. aegypti: the presumed ancestral form Ae. aegypti formosus (Aaf), a sylvan mosquito inhabiting forest habitats in sub-Saharan Africa; and Ae. aegypti aegypti (Aaa), found circumglobally in tropical and subtropical regions in close association with humans. We have been studying gene flow, vector competence and the distribution of Aaa and Aaf in Senegal. We present data that show a northwest-southeast cline in the abundance of the two subspecies. Northwest collections consist of only Aaa while collections in the southeast are all Aaf. The two subspecies were sympatric in six tall grass savanna and scrub sites in central Senegal. Consistent with the literature, competence for DENV2 is correlated with the distribution of the subspecies. Northwestern Aaa collections have a high disseminated infection rate (DIR) while southeast Aaf collections have a low DIR associated with a midgut escape barrier for DENV2. Curiously, our data and a recent publication suggest continuous gene flow across all geographic locations and subspecies in Senegal. This presents a paradox: How can the distribution of vector competence and subspecies be regional when gene flow is continuous? We present exciting data from a QTL mapping experiment gone wrong that demonstrate reduced recombination in Aaa/Aaf hybrids, consistent with an hypothesis that chromosomal inversions exist between the two subspecies. Inversions would allow for gene flow between subspecies while preserving associations in subspecies between morphological markers and vector competence. The possibility of inversions in Ae. aegypti s.l. has been discussed but never proven due to an inability to accurately resolve their polytene chromosomes. Our specific aims are to generate an intensive linkage map of Aaf to define presumptive inversions. Markers arising from this map will be used to define the geographic distribution of inversions in Senegal. We then propose to map Aaf QTL that condition susceptibility to DENV2 and YFV. We also plan to visit 50 additional sites in Senegal not covered in our initial survey to provide a more thorough coverage of vector competence and the prevalence of the subspecies. PUBLIC HEALTH RELEVANCE Reduction of yellow fever and dengue fever in humans is dependent on control of the mosquito Aedes aegypti. Genetic studies that offer insight into vector competence (i.e., the ability to carry and transmit virus) of this species group can more effectively target competent populations. Data suggest gene flow is rapid among geographically distinct populations of Aedes aegypti in Senegal, West Africa. But vector competence and the proportions of the Ae. aegypti aegypti and Ae. aegypti formosus subspecies differ among these same populations. Chromosomal inversions would allow gene flow between subspecies in this region while retaining subspecific morphological characteristics and vector competence. We propose to map the distribution and competence of Aedes aegypti in Senegal, identify the presumptive inversions, and use the genetic markers identified in association with these inversions to map the occurrence of these inversions in Senegal.

描述（由申请人提供）：Aedes aegypti sensu latu（s.l.）是黄热病病毒（YFV）和四种血清型登革热病毒（DENV 1 -4）的主要人类载体。在没有获得许可的DENV疫苗的情况下，尽管存在安全有效的YFV疫苗，但这些疾病的控制仍然主要依赖于媒介控制。我们的长期目标是增加对当地人口动态的了解，以制定更有针对性、更适当、更有希望的可持续控制战略。有两个已知的亚种Ae。埃及人：推测的埃及人祖先的形式。aegypti formosus（Aaf），一种栖息在撒哈拉以南非洲森林栖息地的森林蚊子;和Ae.埃及伊蚊（Aaa），分布于热带和亚热带地区，与人类关系密切。我们一直在研究基因流，载体能力和分布的Aaa和Aaf在塞内加尔。我们目前的数据显示，西北-东南渐变的丰富的两个亚种。西北部的收藏品只有Aaa，而东南部的收藏品都是Aaf。这两个亚种同域分布在6个高草稀树草原和灌木丛在塞内加尔中部的网站。与文献一致，DENV 2的能力与亚种的分布相关。西北部的Aaa集合具有高的播散性感染率（EAE），而东南部的Aaf集合具有与DENV 2的中肠逃逸屏障相关的低EAE。奇怪的是，我们的数据和最近的一份出版物表明，在塞内加尔的所有地理位置和亚种之间都有持续的基因流动。这就提出了一个悖论：当基因流动是连续的时，媒介能力和亚种的分布怎么可能是区域性的？我们提出了令人兴奋的数据，从QTL定位实验出错，证明减少重组Aaa/Aaf杂交，染色体倒位存在于两个亚种之间的假设是一致的。倒位将允许亚种之间的基因流动，同时保留亚种中形态标记和载体能力之间的关联。的可能性倒置在Ae。埃及公司已经讨论过，但从未得到证实，由于无法准确地解决他们的多线染色体。我们的具体目标是产生一个密集的连锁图AAF定义推定倒置。从这张地图上产生的标记将用于确定塞内加尔倒位的地理分布。然后，我们建议定位Aaf QTL，条件对DENV 2和YFV的易感性。我们还计划访问塞内加尔初步调查中未涵盖的另外50个地点，以更全面地了解病媒能力和亚种的流行情况。公共卫生相关性人类黄热病和登革热的减少取决于对埃及伊蚊的控制。遗传研究提供了对载体能力的深入了解（即，携带和传播病毒的能力）可以更有效地针对有能力的种群。数据表明，在西非塞内加尔的埃及伊蚊地理上不同的种群之间，基因流动很快。但是载体的能力和Ae的比例。埃及伊蚊Aegypti aegypti和埃及伊蚊Ae.台湾埃及伊蚊亚种在这些相同的种群中存在差异。染色体倒位将允许该区域亚种间的基因流动，同时保留亚种的形态特征和载体能力。我们建议绘制埃及伊蚊在塞内加尔的分布和能力，确定推定的倒置，并使用与这些倒置相关联的遗传标记来绘制这些倒置在塞内加尔的发生。