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

描述（由申请人提供）：埃及感蚊是黄热病病毒（YFV）和四种血清型登革热病毒（DENV1-4）向人类传播的主要媒介。没有获得许可的DENV疫苗，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病媒控制。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、更有希望可持续的控制战略。伊蚊有两个公认的亚种。埃及伊蚊：假定为伊蚊的祖先。台湾埃及伊蚊（Aaf），一种生活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），分布于全球热带和亚热带地区，与人类关系密切。我们一直在研究Aaa和Aaf在塞内加尔的基因流、载体能力和分布。我们提供的数据显示，这两个亚种的丰度呈西北-东南倾斜。西北地区的藏品只有Aaa，而东南地区的藏品都是Aaf。这两个亚种在塞内加尔中部的6个高草稀树草原和灌丛地点是同域的。与文献一致，对DENV2的能力与亚种的分布有关。西北地区的Aaa收集具有高播散性感染率（DIR），而东南地区的Aaf收集具有与DENV2中肠逃逸屏障相关的低DIR。奇怪的是，我们的数据和最近发表的一篇文章表明，基因在塞内加尔所有地理位置和亚种之间持续流动。这就提出了一个悖论：当基因流是连续的时，媒介能力和亚种的分布怎么可能是区域性的？我们从一个出错的QTL定位实验中获得了令人兴奋的数据，证明Aaa/Aaf杂交种的重组减少，这与两个亚种之间存在染色体倒位的假设一致。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联系。Ae中反转的可能性。埃及伊蚊（Aegypti s.l.）曾被讨论过，但由于无法准确地分辨它们的多染色体，因此从未得到证实。我们的具体目标是生成Aaf的密集链接图，以定义推定倒置。从该地图中产生的标记将用于确定塞内加尔逆温的地理分布。然后，我们提出绘制对DENV2和YFV易感性的Aaf QTL。我们还计划访问塞内加尔最初调查未涵盖的另外50个地点，以更全面地了解病媒能力和亚种流行情况。减少人间黄热病和登革热取决于对埃及伊蚊的控制。对该物种群的媒介能力（即携带和传播病毒的能力）提供深入了解的遗传研究可以更有效地针对有能力的种群。数据显示，西非塞内加尔的埃及伊蚊在地理上不同的种群中基因流动迅速。但是向量能力和Ae的比例。埃及伊蚊和埃及伊蚊。台湾埃及伊蚊亚种在这些相同的种群中有所不同。染色体倒位将允许该区域亚种之间的基因流动，同时保留亚种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图，确定假定的倒置，并利用与这些倒置相关的遗传标记来绘制这些倒置在塞内加尔的发生情况。

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.