The impact of artificial selection for Wolbachia-mediated dengue virus blocking on phage WO.
The impact of artificial selection for Wolbachia-mediated dengue virus blocking on phage WO.
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DOI：
10.1371/journal.pntd.0009637
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发表时间：
2021-07
影响因子：
3.8
通讯作者：
McGraw EA
中科院分区：
文献类型：
--
作者：
Dutra HLC;Ford SA;Allen SL;Bordenstein SR;Chenoweth SF;Bordenstein SR;McGraw EA
沃尔巴克氏菌目前处于控制埃及伊蚊媒介虫媒病毒传播的全球努力的前沿。沃尔巴克氏菌的使用依赖于两种表型--由原噬菌体WO中的CifA和cifB基因引起的细胞质不亲和性(CI)和Wolbachia介导的病原体阻断(WMPB)。这些特点使当地，自我维持的减少传播登革热(DENV)后，释放沃尔巴克氏感染埃及伊蚊。在这里，借助于先前的人工选择实验，产生了低和高病原菌阻断系，我们检查了WMPB和噬菌体WO之间的潜在联系。我们没有发现证据表明沃尔巴克氏菌或噬菌体WO的相对密度可以预测选定品系的DENV阻断强度。然而，对于WMPB低的品系，选择导致噬菌体WO相对密度降低。低阻塞线之前被证明由于选择而降低了适合度。通过随后的基因组分析，我们证明了支持低阻断选择的SNP变异导致了1号染色体上潜在有害SNPs频率的增加。1号染色体上的关键区域包含与细胞周期调节、氧化应激、转录暂停等相关的基因，这些基因可能对Wolbachia细胞内环境产生级联效应。我们假设，噬菌体WO的减少可能是由于直接被选择为阻断的基因座的变化，或者是由于搭便车导致与阻断基因连锁不平衡的预测有害等位基因的积累。对于噬菌体WO较少的低株系，我们还检测到CIFA和CIFB CI基因的表达降低，其表达模式在体细胞和生殖组织之间存在差异。综上所述，我们认为对WMPB性状的人工选择对噬菌体WO密度和CI致病基因的转录都有相应的影响。未来的研究可能包括更详细地分析埃及斑潜蝇1‘染色体S影响白蛋白B的能力以及其他与沃尔巴克氏菌相关的内在因素，如噬菌体WO。沃尔巴克氏菌是一种广泛存在于昆虫体内的共生菌，可引起沃尔巴克氏菌介导的病原菌阻断(WMPB)和细胞质不亲和性(CI)。后者由CIF基因介导，定位于原噬菌体WO区。正因为如此，感染了沃尔巴克氏菌的蚊子目前正在野外被用来对抗登革热(DENV)等媒介传播病毒向人类群体的传播。借助于先前的人工选择实验，产生了具有可变(高和低)DENV阻断强度的品系，我们测试了WMPB和噬菌体WO之间的潜在联系。没有证据表明沃尔巴克氏菌和噬菌体WO密度可以预测DENV的阻断强度。然而，我们发现低阻断线降低了噬菌体WO密度，并以组织特异性的方式降低了cif基因的表达。我们证明，除了先前报道的适合度降低外，低阻断系还表现出1号染色体上潜在有害SNPs频率的增加。我们的假设是，噬菌体WO的减少可能是由于直接选择阻断的座位发生了变化，或者是与蚊子预测的有害等位基因的积累有关的连锁不平衡事件所致。我们的结果强调了1号染色体对WMPB的重要性，以及它对其他沃尔巴克氏菌相关因子(如噬菌体WO)的潜在影响。
Wolbachia is currently at the forefront of global efforts to control arbovirus transmission from the vector Aedes aegypti. The use of Wolbachia relies on two phenotypes—cytoplasmic incompatibility (CI), conferred by cifA and cifB genes in prophage WO, and Wolbachia-mediated pathogen blocking (WMPB). These traits allow for local, self-sustaining reductions in transmission of dengue (DENV) following release of Wolbachia-infected A. aegypti. Here, aided by previous artificial selection experiment that generated Low and High pathogen blocking lines, we examined the potential link between WMPB and phage WO. We found no evidence that Wolbachia or phage WO relative densities predict DENV blocking strength across selected lines. However, selection resulted in reduced phage WO relative density for the Low WMPB line. The Low blocking line was previously shown to have reduced fitness as a result of selection. Through subsequent genomic analyses, we demonstrate that SNP variation underpinning selection for low blocking led to elevated frequency of potential deleterious SNPs on chromosome 1. The key region on chromosome 1 contains genes relating to cell cycle regulation, oxidative stress, transcriptional pausing, among others, that may have cascading effects on Wolbachia intracellular environment. We hypothesize that reduction in phage WO may be driven by changes in the loci directly under selection for blocking, or by the accumulation of predicted deleterious alleles in linkage disequilibrium with blocking loci resulting from hitchhiking. For the Low line with fewer phage WO, we also detected reduced expression of cifA and cifB CI genes, with patterns of expression varying between somatic and reproductive tissues. In conclusion, we propose that artificial selection for WMPB trait had corresponding impacts on phage WO densities, and also the transcription of CI-causing genes. Future studies may include a more detailed analysis of the regions the A. aegypti chromosome 1’s ability to affect WMPB and other Wolbachia-associated intrinsic factors such as phage WO. Wolbachia are widespread endosymbiotic bacteria of insects that cause Wolbachia-mediated pathogen blocking (WMPB) and cytoplasmic incompatibility (CI). The latter mediated by cif genes localized in the prophage WO region. Because of that, Wolbachia-infected mosquitoes are currently being used in field to fight the transmission of vector-borne viruses such as Dengue (DENV) to human populations. Aided by a previous artificial selection experiment that generated lines with variable (High and Low) DENV blocking strength, we tested for a potential link between WMPB and phage WO. There was no evidence that Wolbachia nor phage WO densities predict DENV blocking strength. However, we found that the Low blocking line had reduced phage WO density, and lower expression of the cif genes in a tissue-specific manner. We demonstrate that in addition to previous report of reduced fitness, the Low blocking line also exhibited increased frequency of potential deleterious SNPs on chromosome 1. Our hypotheses are that reduction in phage WO may have resulted from changes in the loci directly under selection for blocking, or by linkage disequilibrium events linked to the accumulation of mosquito predicted deleterious alleles. Our results highlight the importance of chromosome 1 for WMPB and its potential impact for other Wolbachia-associated factors like phage WO.
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