Wolbachia-induced enhancement of human arboviral pathogens

 描述(申请人提供)：杀虫剂抗药性的演变和药物治疗的失败阻碍了控制媒介传播病原体的努力。为了提高控制工作的可持续性和有效性，正在考虑替代媒介控制战略。感染母系遗传的内共生菌Wolbachia limientis已被证明能抑制病媒节肢动物中的病毒和寄生虫。感染沃尔巴克氏菌的蚊子目前正被释放到大自然中，以控制人类疾病。然而，一个令人担忧的趋势正在出现，沃尔巴克氏菌感染会增强而不是抑制昆虫媒介中的病原体。我们现在首次证明了沃尔巴克氏菌介导的人类病原体(西尼罗河病毒)在蚊子媒介中的增强；这是一个发人深省的提醒，一些昆虫中沃尔巴克氏菌感染所产生的病原体抑制效应不能也不应该在媒介-病原体系统中推广。了解沃尔巴克氏菌引起的病原菌增强的一般程度以及导致这种表型的机制(S)对于估计基于沃尔巴克氏菌的控制策略失败或使事情变得更糟的可能性、识别基于沃尔巴克氏菌的控制可能在现场失效的潜在点以及在发生不可预见的有害后果的情况下规划风险缓解策略至关重要。在这项研究中，我们将研究沃尔巴克氏杆菌对蚊子全息组的调节可以导致虫媒病毒在一些对人类具有重要意义的病原体系统中感染/传播增加的假设。这一假设将在以下三个具体目标中得到验证：(1)确定沃尔巴克氏菌诱导的虫媒病毒在多个蚊子病原体系统中增强的共性；(2)确定沃尔巴克氏菌-微生物组相互作用在介导CX中西尼罗河病毒增强中的作用。(3)确定沃尔巴克氏菌诱导的蚊子基因转录调控在介导西尼罗河病毒在CX中增强中的作用。塔沙利酒。

 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 for the first time Wolbachia-mediated enhancement of a human pathogen (West Nile virus) in a 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 extent of Wolbachia-induced pathogen enhancement, and the mechanism(s) leading to this phenotype 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 the 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.