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（由申请人提供）：杀虫剂耐药性的进化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，正在考虑采用母系遗传感染的替代媒介控制策略。内共生沃尔巴克氏体已被证明可以抑制媒介节肢动物中的病毒和寄生虫，目前正将感染沃尔巴克氏体的蚊子释放到自然界中以控制人类疾病。一种令人担忧的趋势正在出现，即沃尔巴克氏体感染在昆虫媒介中表现出而不是抑制病原体，我们现在已经了解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，以及导致蚊子中几种虫媒病毒人类病原体的这种表型增强的机制。跗库蚊；一个清醒的提醒是，沃尔巴克氏体感染对某些昆虫产生的病原体抑制作用不能也不应该推广到媒介病原体系统中，这对于了解一般情况至关重要。估计基于沃尔巴克氏体的控制策略失败或使情况变得更糟的可能性，识别基于沃尔巴克氏体的控制可能在现场崩溃的潜在点，以及在出现不可预见的有害结果时规划风险缓解策略。研究中，我们将研究沃尔巴克氏体诱导的蚊子全基因组调节可能导致某些对人类重要的媒介病原体系统中虫媒病毒感染/传播增加的假设，该假设将在以下三个具体部分中进行检验。目的：(1) 确定沃尔巴克氏体诱导的虫媒病毒在多种蚊子病原体系统中增强的普遍性；(2) 确定沃尔巴克氏体-微生物组相互作用在介导跗节中 WNV 增强中的作用；诱导调节蚊子基因转录介导 Cx 中 WNV 增强。