Assessing the genetic basis of arboviral salivary gland escape barriers in Aedes aegypti.

评估埃及伊蚊虫媒病毒唾液腺逃逸障碍的遗传基础。

• 批准号: 9227152
• 负责人: WILLIAM C. BLACK
• 金额: $ 18.88万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-02 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9227152
• 关键词: Aedes; Affect; African; Alphavirus; American; Arboviruses; Asian Americans; Asians; Biological Assay; Breeding; Bunyaviridae; Chest; Culicidae; Data; Dengue Hemorrhagic Fever; Dengue Virus; Disease Outbreaks; Dose; Environmental Risk Factor; Experimental Designs; Female; Flavivirus; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Genotype; Geographic state; Gland; Head; Heritability; Immune system; Indian Ocean; Infection; Investigation; Leg; Malaysia; Measures; Methods; Mexican; Mexico; Midgut; Mothers; Nucleic Acids; Oils; Organ; Orthobunyavirus; Partner in relationship; Pharmacologic Substance; Play; Population; Quantitative Genetics; RNA; Reporting; Research Personnel; Role; Saliva; Salivary Glands; Senegal; Serotyping; South African; South America; Sucrose; Technology; Testing; Time; Tissues; Titrations; Transgenic Organisms; Variant; Viral; Virus; Virus Diseases; Work; Yellow Fever; Zika Virus; base; chikungunya; design; male; novel strategies; offspring; tissue culture; tool; transmission process; vector; viral RNA; viral transmission

PROJECT SUMMARY / ABSTRACT The salivary gland is the organ that ultimately transmits an arbovirus from an infected mosquito into her vertebrate host. Salivary gland infection barriers (SGIBs) and salivary gland escape barriers (SGEBs) determine whether the saliva of a mosquito will contain sufficient virus to overcome the vertebrate immune system. SGIBs are manifest as the absence of detectable virus in the salivary glands of mosquitoes that have a disseminated viral infection (as determined by bioassay of pulled legs or smashed heads). There are large numbers of studies that document SGIBs for bunyaviruses and flaviviruses. SGEBs on the other hand are manifest as the absence of detectable virus in the saliva of mosquitoes that have infected salivary glands (as determined by bioassay of dissected glands). In contrast to SGIBs, there are very few studies that document SGEBs in mosquitoes and those have only examined bunyaviruses. Furthermore these SGEB studies were not performed in genetically “tractable” mosquito species that can be easily colonized from the field, reared in the lab, crossed as single pairs and have an abundance of genetic markers. Because of this deficiency we have little understanding of whether there is a genetic basis for SGEBs or whether they are random, subject to a few or many “environmental” factors. The results of this study will indicate whether there are genetic factors in the mosquito which, if manipulated through transgenics or pharmaceuticals, could interfere with the ability of the mosquito to transmit an arbovirus. Alternatively if mosquito genetics accounts for very little of the ability of the mosquito to transmit arboviruses then this is unlikely to be a fruitful approach. PI Black's earlier work on the quantitative genetics of DENV-2 in Ae. aegypti midgut infection and escape barriers indicated that 40% of the variation was due to genetic effects and 60% was due to environmental effects. To date, many genes have been identified that affect tissue barriers to DENV-2 infections but many environmental effects (including viral genotype) have also been identified. Will the same hold true from SGIBs and SGEBs?

项目概要/摘要 唾液腺是最终传播感染者虫媒病毒的器官 蚊子进入她的脊椎动物宿主。唾液腺感染屏障（SGIB）和唾液腺 逃逸屏障（SGEB）确定蚊子的唾液是否含有足够的病毒 克服脊椎动物的免疫系统。 SGIB 表现为缺乏可检测到的 具有传播性病毒感染的蚊子唾液腺中的病毒（如 通过拉腿或打碎头的生物测定来确定）。有大量的研究 记录了布尼亚病毒和黄病毒的 SGIB。另一方面，SGEB 是显而易见的 因为在感染唾液腺的蚊子的唾液中没有检测到病毒 （通过解剖腺体的生物测定确定）。与 SGIB 相比，很少有 记录蚊子中 SGEB 的研究以及仅检查布尼亚病毒的研究。 此外，这些 SGEB 研究并不是在基因上“易驯服”的蚊子物种中进行的 可以很容易地从田间定植，在实验室饲养，单对杂交，并具有 丰富的遗传标记。由于这一缺陷，我们对此知之甚少。 SGEB 是否有遗传基础，或者它们是否是随机的，受到一些或 诸多“环境”因素。这项研究的结果将表明是否存在遗传因素 蚊子中的一些因素，如果通过转基因或药物进行操纵，可以 干扰蚊子传播虫媒病毒的能力。或者如果有蚊子 遗传学对蚊子传播虫媒病毒的能力影响很小，那么这是 不太可能是一个富有成果的方法。 PI Black 早期关于 DENV-2 数量遗传学的研究 在Ae。埃及伊蚊中肠感染和逃逸屏障表明 40% 的变异是由于 遗传影响占60%，环境影响占60%。迄今为止，许多基因已被 已确定影响 DENV-2 感染的组织屏障，但也有许多环境影响 （包括病毒基因型）也已被鉴定。 SGIB 和 SGEB？