Wolbachia-induced enhancement of human arboviral pathogens

 描述（由申请方提供）：杀虫剂耐药性的演变和药物治疗的失败阻碍了控制病媒传播病原体的努力。为了提高控制工作的可持续性和效力，正在考虑采用其他病媒控制战略。感染母系遗传的内共生体Wolbachia pipientis已被证明可以抑制载体节肢动物中的病毒和寄生虫。受沃尔巴克氏体感染的蚊子目前正被释放到自然界以控制人类疾病。然而，一个令人担忧的趋势正在出现，即沃尔巴克氏体感染增强而不是抑制昆虫媒介中的病原体。我们现在已经证明了沃尔巴克氏体介导的沃尔巴克氏体诱导的病原体增强的程度，以及导致蚊子载体淡色库蚊中的几种虫媒病毒人类病原体的这种表型增强的机制;清醒地提醒人们，在一些昆虫中由沃尔巴克氏体感染引起的病原体抑制作用不能也不应该在整个载体-病原体系统中推广。了解一般是至关重要的估计有多大可能沃尔巴克氏体为基础的控制策略是失败或使事情变得更糟，为确定潜在的点，其中沃尔巴克氏体为基础的控制可能会打破在现场，并为规划风险缓解策略，在他的情况下不可预见的有害结果。在这项研究中，我们将调查的假设，沃尔巴克氏体诱导的调制的蚊子全基因组可能会导致增加虫媒病毒感染/传播的一些载体病原体系统的人类的重要性。将在以下三个具体目的中检验该假设：（1）确定在多种蚊子-病原体系统中沃尔巴克氏体诱导的虫媒病毒增强的一般性;（2）确定沃尔巴克氏体-微生物组相互作用在介导Cx中的WNV增强中的作用。（3）确定Wolbachia诱导的蚊子基因转录调节在介导Cx中WNV增强中的作用。跗骨

 DESCRIPTION (provided by applicant): Efforts to control vector-borne pathogens have been hindered by evolution of insecticide resistance and failing drug therapies. To improve the sustainability and efficacy of control efforts, alternative vector control strategies are being considered. Infection with the maternally inherited endosymbiont Wolbachia pipientis has been demonstrated to inhibit viruses and parasites in vector arthropods. Wolbachia-infected mosquitoes are currently being released into nature to control human disease. However, a worrying trend is emerging whereby Wolbachia infections enhance rather than suppress pathogens in insect vectors. We have now demonstrated Wolbachia-mediated extent of Wolbachia-induced pathogen enhancement, and the mechanism(s) leading to this phenotype enhancement of several arboviral human pathogens in the mosquito vector Culex tarsalis; a sobering reminder that the pathogen inhibitory effects resulting from Wolbachia infection in some insects cannot and should not be generalized across vector-pathogen systems. Understanding the general are critical for estimating how likely Wolbachia-based control strategies are to fail or make things worse, for identifying potential points where Wolbachia-based control is likely to break down in the field, and for planning risk mitigation strategies in he case of unforeseen harmful outcomes. In this research, we will investigate the hypothesis that Wolbachia-induced modulation of the mosquito hologenome can lead to increased arbovirus infection/transmission in some vector-pathogen systems of human importance. This hypothesis will be examined in the following three Specific Aims: (1) Determine the generality of Wolbachia- induced arbovirus enhancement in multiple mosquito-pathogen systems; (2) Determine the role of Wolbachia- microbiome interactions in mediating WNV enhancement in Cx. tarsalis; (3) Determine the role of Wolbachia- induced modulation of mosquito gene transcription in mediating WNV enhancement in Cx. tarsalis.