School of Biological Sciences, Monash University, Clayton, Melbourne, VIC, Australia.
School of Biological Sciences, The University of Queensland, QLD, St. Lucia, Australia.
Parasit Vectors. 2017 Dec 28;10(1):622. doi: 10.1186/s13071-017-2589-3.
The mosquito vector Aedes aegypti is responsible for transmitting a range of arboviruses including dengue (DENV) and Zika (ZIKV). The global reach of these viruses is increasing due to an expansion of the mosquito's geographic range and increasing urbanization and human travel. Vector control remains the primary means for limiting these diseases. Wolbachia pipientis is an endosymbiotic bacterium of insects that has the ability to block the replication of pathogens, including flaviviruses such as DENV or ZIKV, inside the body of the vector. A strain of Wolbachia called wMel is currently being released into wild mosquito populations to test its potential to limit virus transmission to humans. The mechanism that underpins the virus blocking effect, however, remains elusive.
We used a modified full-sib breeding design in conjunction with vector competence assays in wildtype and wMel-infected Aedes aegypti collected from the field. All individuals were injected with DENV-2 intrathoracically at 5-6 days of age. Tissues were dissected 7 days post-infection to allow quantification of DENV and Wolbachia loads.
We show the first evidence of family level variation in Wolbachia-mediated blocking in mosquitoes. This variation may stem from either genetic contributions from the mosquito and Wolbachia genomes or environmental influences on Wolbachia. In these families, we also tested for correlations between strength of blocking and expression level for several insect immunity genes with possible roles in blocking, identifying two genes of interest (AGO2 and SCP-2).
In this study we show variation in Wolbachia-mediated DENV blocking in Aedes aegypti that may arise from genetic contributions and environmental influences on the mosquito-Wolbachia association. This suggests that Wolbachia-mediated blocking may have the ability to evolve through time or be expressed differentially across environments. The long-term efficacy of Wolbachia in the field will be dependent on the stability of blocking. Understanding the mechanism of blocking will be necessary for successful development of strategies that counter the emergence of evolved resistance or variation in its expression under diverse field conditions.
病媒蚊埃及伊蚊是传播多种虫媒病毒的媒介，包括登革热（DENV）和寨卡（ZIKV）病毒。由于蚊子地理分布范围的扩大、城市化和人类旅行的增加，这些病毒的全球传播范围也在不断扩大。病媒控制仍然是限制这些疾病的主要手段。沃尔巴克氏体是一种昆虫共生菌，具有阻止病原体（包括登革热病毒或寨卡病毒等黄病毒）在媒介体内复制的能力。一种名为 wMel 的沃尔巴克氏体菌株目前正在被释放到野生蚊子种群中，以测试其限制病毒向人类传播的潜力。然而，支撑这种病毒阻断效应的机制仍然难以捉摸。
我们使用改良的全同胞繁殖设计，并结合从野外收集的野生型和 wMel 感染的埃及伊蚊的媒介效能测定。所有个体在 5-6 天大时经胸部注射 DENV-2。在感染后 7 天进行组织解剖，以量化 DENV 和沃尔巴克氏体的负荷。
我们首次证明了蚊子中沃尔巴克氏体介导的阻断存在家族水平的变异。这种变异可能源于蚊子和沃尔巴克氏体基因组的遗传贡献，或环境对沃尔巴克氏体的影响。在这些家族中，我们还测试了几个可能在阻断中起作用的昆虫免疫基因的表达水平与阻断强度之间的相关性，确定了两个感兴趣的基因（AGO2 和 SCP-2）。
在这项研究中，我们表明埃及伊蚊中沃尔巴克氏体介导的 DENV 阻断存在变异，这种变异可能源于蚊子-沃尔巴克氏体共生体的遗传贡献和环境影响。这表明，沃尔巴克氏体介导的阻断可能具有随时间进化或在不同环境中表现出差异表达的能力。沃尔巴克氏体在野外的长期疗效将取决于阻断的稳定性。了解阻断机制对于成功制定应对进化抗性出现或其在不同野外条件下表达变化的策略是必要的。
