PDF(Pubmed)
Abstract：
Vector competence defines the ability of a vector to acquire, host, and transmit a pathogen. Understanding the molecular determinants of the mosquitos\' competence to host dengue virus (DENV) holds promise to prevent its transmission. To this end, we employed RNA-seq to profile mRNA transcripts of the female Aedes aegypti mosquitos feeding on naïve vs viremic mouse. While most transcripts (12,634) did not change their abundances, 360 transcripts showed decreases. Biological pathway analysis revealed representatives of the decreased transcripts involved in the wnt signaling pathway and hippo signaling pathway. One thousand three hundred fourteen transcripts showed increases in abundance and participate in 21 biological pathways including amino acid metabolism, carbon metabolism, fatty acid metabolism, and oxidative phosphorylation. Inhibition of oxidative phosphorylation with antimycin A reduced oxidative phosphorylation activity and ATP concentration associated with reduced DENV replication in the Aedes aegypti cells. Antimycin A did not affect the amounts of the non-structural proteins 3 and 5, two major components of the replication complex. Ribavirin, an agent that reduces GTP concentration, recapitulated the effects of reduced ATP concentration on DENV replication. Knocking down one of the oxidative phosphorylation components, ATP synthase subunit β, reduced DENV replication in the mosquitos. In summary, our results suggest that DENV enhances metabolic pathways in the female Aedes aegypti mosquitos to supply nutrients and energy for virus replication. ATP synthase subunit β knockdown might be exploited to reduce the mosquitos\' competence to host and transmit DENV.
OBJECTIVE: Through evolution, the mosquito-borne viruses have adapted to the blood-feeding behaviors of their opportunist hosts to fulfill a complete lifecycle in humans and mosquitos. Disruption in the mosquitos\' ability to host these viruses offers strategies to prevent diseases caused by them. With the advent of genomic tools, we discovered that dengue virus (DENV) benefited from the female mosquitos\' bloodmeals for metabolic and energetic supplies for replication. Chemical or genetic disruption in these supplies reduced DENV replication in the female mosquitos. Our discovery can be exploited to produce genetically modified mosquitos, in which DENV infection leads to disruption in the supplies and thereby reduces replication and transmission. Our discovery might be extrapolated to prevent mosquito-borne virus transmission and the diseases they cause.
OBJECTIVE: Through evolution, the mosquito-borne viruses have adapted to the blood-feeding behaviors of their opportunist hosts to fulfill a complete lifecycle in humans and mosquitos. Disruption in the mosquitos\' ability to host these viruses offers strategies to prevent diseases caused by them. With the advent of genomic tools, we discovered that dengue virus (DENV) benefited from the female mosquitos\' bloodmeals for metabolic and energetic supplies for replication. Chemical or genetic disruption in these supplies reduced DENV replication in the female mosquitos. Our discovery can be exploited to produce genetically modified mosquitos, in which DENV infection leads to disruption in the supplies and thereby reduces replication and transmission. Our discovery might be extrapolated to prevent mosquito-borne virus transmission and the diseases they cause.
摘要：
矢量能力定义了矢量获取的能力，host,并传播病原体。了解蚊子对登革热病毒（DENV）的宿主能力的分子决定因素有望防止其传播。为此,我们使用RNA-seq对在未感染病毒小鼠上喂食的雌性埃及伊蚊的mRNA转录本进行了分析。虽然大多数成绩单（12,634）没有改变它们的丰度，360个转录本显示减少。生物学途径分析揭示了wnt信号途径和hippo信号途径中涉及的转录物减少的代表。一千三百十四个转录本显示丰度增加，并参与21个生物学途径，包括氨基酸代谢，碳代谢，脂肪酸代谢，和氧化磷酸化。用抗霉素A抑制氧化磷酸化降低了与埃及伊蚊细胞中DENV复制减少相关的氧化磷酸化活性和ATP浓度。抗霉素A不影响复制复合物的两个主要成分非结构蛋白3和5的量。利巴韦林,一种降低GTP浓度的药剂,概述了降低ATP浓度对DENV复制的影响。敲除氧化磷酸化成分之一，ATP合酶亚基β,减少蚊子中DENV的复制。总之,我们的结果表明DENV增强了雌性埃及伊蚊的代谢途径，为病毒复制提供营养和能量。ATP合酶亚基β敲低可能被用来降低蚊子宿主和传播DENV的能力。
目标：通过进化，蚊子传播的病毒已经适应了其机会主义宿主的采血行为，以满足人类和蚊子的完整生命周期。破坏蚊子宿主这些病毒的能力提供了预防由它们引起的疾病的策略。随着基因组工具的出现，我们发现，登革热病毒（DENV）受益于雌性蚊子的血液中的代谢和能量供应的复制。这些供应中的化学或遗传破坏减少了雌性蚊子的DENV复制。我们的发现可以用来生产转基因蚊子，其中DENV感染导致供应中断，从而减少复制和传播。我们的发现可能被推断为防止蚊媒病毒传播及其引起的疾病。
目标：通过进化，蚊子传播的病毒已经适应了其机会主义宿主的采血行为，以满足人类和蚊子的完整生命周期。破坏蚊子宿主这些病毒的能力提供了预防由它们引起的疾病的策略。随着基因组工具的出现，我们发现，登革热病毒（DENV）受益于雌性蚊子的血液中的代谢和能量供应的复制。这些供应中的化学或遗传破坏减少了雌性蚊子的DENV复制。我们的发现可以用来生产转基因蚊子，其中DENV感染导致供应中断，从而减少复制和传播。我们的发现可能被推断为防止蚊媒病毒传播及其引起的疾病。
