Wolbachia-induced enhancement of human arboviral pathogens

沃尔巴克氏体诱导的人类虫媒病毒病原体增强

• 批准号: 9217559
• 负责人: Jason L Rasgon
• 金额: $ 38.28万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9217559
• 关键词: Aedes; Affect; Arbovirus Infections; Arboviruses; Arthropod Vectors; Bacteria; Candidate Disease Gene; Culex (Genus); Culex pipiens; Culicidae; Data; Encephalitis Viruses; Environment; Evolution; Gene Expression; Genes; Genetic; Genetic Transcription; Human; Infection; Inherited; Insect Vectors; Insecta; Insecticide Resistance; Lacrosse; Lead; Mediating; Nature; Outcome; Parasites; Pattern; Pharmacotherapy; Phenotype; Pseudomonas; Public Relations; Refractory; Research; Resistance; Rift Valley fever virus; Role; Sindbis Virus; System; Time; Virus; West Nile virus; Wolbachia; base; endosymbiont; genetic approach; human disease; improved; microbiome; microorganism; novel; pathogen; public health relevance; response; reverse genetics; risk mitigation; sobriety; transcriptome sequencing; transmission process; trend; vector; vector control; vector mosquito; vector transmission

 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.

 描述（由适用提供）：控制媒介传播病原体的努力受到杀虫剂耐药性和药物疗法失败的发展的阻碍。为了提高控制努力的可持续性和效率，正在考虑替代媒介控制策略。已经证明，主要遗传的内共生膜沃尔巴奇植物的感染已被证明可以抑制载体节肢动物中的病毒和寄生虫。沃尔巴契亚感染的蚊子目前正在释放到自然中以控制人类疾病。然而，令人担忧的趋势正在出现，从而使沃尔巴氏菌感染增强而不是抑制昆虫载体中的病原体。现在，我们已经证明了沃尔巴奇介导的沃尔巴基亚诱导的病原体增强的程度，以及导致这种表型增强的机制，增强了蚊子载体库克莱克斯·塔尔萨里斯（Coulex Tarsalis）的几种arboviral人类病原体的增强。这是一个清醒的提醒，在某些昆虫中因沃尔巴奇感染引起的病原体抑制作用不能也不应在载体 - 病原体系统上推广。了解一般对于估计沃尔巴契亚的控制策略失败或使情况变得更糟的可能性至关重要，对于确定基于沃尔巴契亚的控制可能会破坏该领域的潜在点，以及在不可预见的有害成果的情况下计划降低风险的策略。在这项研究中，我们将调查以下假设：沃尔巴奇诱导的蚊子全息组的调节可以导致某些人类重要性的一些载体 - 病原体系统中的Arbovirus感染/传播增加。该假设将在以下三个特定目的中进行检查：（1）确定多个蚊子 - 病原体系统中沃尔巴基亚诱导的Arbovirus增强的通用性； （2）确定Wolbachia-Microbiome相互作用在CX中介导WNV增强中的作用。塔萨里斯； （3）确定Wolbachia诱导的蚊子基因转录调节在CX中介导WNV增强中的作用。塔萨里斯。