Department of Entomology, Center for Infectious Disease Dynamics, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
School of Biological Sciences, Monash University, Melbourne, Victoria, Australia.
Nat Microbiol. 2019 Nov;4(11):1832-1839. doi: 10.1038/s41564-019-0533-3. Epub 2019 Aug 26.
The dengue, Zika and chikungunya viruses are transmitted by the mosquito Aedes aegypti and pose a substantial threat to global public health. Current vaccines and mosquito control strategies have limited efficacy, so novel interventions are needed. Wolbachia are bacteria that inhabit insect cells and have been found to reduce viral infection-a phenotype that is referred to as viral 'blocking'. Although not naturally found in A. aegypti, Wolbachia were stably introduced into this mosquito in 2011 and were shown to reduce the transmission potential of dengue, Zika and chikungunya. Subsequent field trials showed Wolbachia's ability to spread through A. aegypti populations and reduce the local incidence of dengue fever. Despite these successes, the evolutionary stability of viral blocking is unknown. Here, we utilized artificial selection to reveal genetic variation in the mosquito that affects Wolbachia-mediated dengue blocking. We found that mosquitoes exhibiting weaker blocking also have reduced fitness, suggesting the potential for natural selection to maintain blocking. We also identified A. aegypti genes that affect blocking strength, shedding light on a possible mechanism for the trait. These results will inform the use of Wolbachia as biocontrol agents against mosquito-borne viruses and direct further research into measuring and improving their efficacy.
登革热、寨卡和基孔肯雅热病毒通过埃及伊蚊传播，对全球公共卫生构成重大威胁。目前的疫苗和蚊虫控制策略效果有限，因此需要新的干预措施。沃尔巴克氏体是一种寄生于昆虫细胞的细菌，已被发现能减少病毒感染——这种表型被称为病毒“阻断”。虽然埃及伊蚊中自然不存在沃尔巴克氏体，但 2011 年，这种细菌被稳定地引入到埃及伊蚊中，并被证明能降低登革热、寨卡和基孔肯雅热病毒的传播潜力。随后的现场试验表明，沃尔巴克氏体能够在埃及伊蚊种群中传播，并降低登革热的本地发病率。尽管取得了这些成功，但沃尔巴克氏体介导的病毒阻断的进化稳定性尚不清楚。在这里，我们利用人工选择揭示了影响沃尔巴克氏体介导的登革热阻断的蚊子中的遗传变异。我们发现，表现出较弱阻断的蚊子其适应性也降低了，这表明自然选择有可能维持阻断。我们还确定了影响阻断强度的埃及伊蚊基因，这为该特性的可能机制提供了线索。这些结果将为利用沃尔巴克氏体作为控制蚊媒病毒的生物防治剂提供信息，并指导进一步研究衡量和提高其功效。
