The Aedes aegypti toll pathway controls dengue virus infection.

The Aedes aegypti toll pathway controls dengue virus infection.
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DOI:
10.1371/journal.ppat.1000098
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发表时间:
2008-07-04
期刊:
影响因子:
6.7
通讯作者:
Dimopoulos, George
Dimopoulos, George
中科院分区:
医学1区
文献类型:
--
作者:
Xi, Zhiyong;Ramirez, Jose L.;Dimopoulos, George

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埃及伊蚊是登革热病毒的蚊子载体,利用其先天免疫系统抵御各种病原体,其中一些病原体可引起人类疾病。迄今为止,昆虫对病毒的先天免疫防御的特征主要在果蝇中进行研究,除了基于RNA干扰的防御系统之外,果蝇似乎还利用不同的免疫途径来对抗不同类型的病毒。我们使用了最近发布的Ae的全基因组序列。埃及蚊子,结合高通量基因表达和RNA干扰(RNAi)为基础的反向遗传分析,以表征其响应登革热病毒感染在不同的身体隔室。我们进一步探讨了蚊子内源性微生物植物群对病毒感染的影响。我们的研究结果表明,Toll通路在调节对登革病毒的抗性中起着重要作用,如几个Toll通路相关基因的感染响应调节和功能评估所示。我们还表明,蚊子的天然微生物群在调节登革病毒感染中发挥作用,可能是通过Toll免疫途径的基础水平刺激。埃及伊蚊主要负责传播导致人类疾病的登革热病毒。这种病毒会被感染的血液吸收,并首先感染蚊子的肠道组织。它会从肠道迁移到蚊子的其他部位,包括唾液腺,在第二次吸血时,它可以从那里传播给另一个人。在这项研究中,我们表明蚊子利用其先天免疫系统来控制登革热病毒感染。病毒感染将导致主要由Toll途径控制的蚊子免疫应答的激活。这些反应需要限制病毒感染的抗病毒活性。我们还表明,蚊子的天然微生物植物群在调节登革热病毒感染中发挥作用,可能是通过刺激蚊子的免疫系统。
Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference–based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi)-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito's endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection-responsive regulation and functional assessment of several Toll pathway–associated genes. We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway. The Aedes aegypti mosquito is largely responsible for the transmission of dengue viruses that cause disease in humans. The virus is taken up with an infected blood meal from which it will first infect the mosquito gut tissue. From the gut it will migrate to other parts of the mosquito, including the salivary glands, from where it can be transmitted to another human upon a second blood meal. In this study we show that the mosquito utilizes its innate immune system to control dengue virus infection. Infection with the virus will result in the activation of mosquito immune responses that are mainly controlled by the Toll pathway. These responses entail antiviral activities that limit infection with the virus. We also show that the mosquito's natural microbial flora play a role in modulating the dengue virus infection, possibly through the stimulation of the mosquito's immune system.
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