Transgenic refractory Aedes aegypti lines are resistant to multiple serotypes of dengue virus.

Transgenic refractory Aedes aegypti lines are resistant to multiple serotypes of dengue virus.
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DOI:
10.1038/s41598-021-03229-4
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发表时间:
2021-12-13
期刊:
影响因子:
4.6
通讯作者:
Chen CH
Chen CH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu WL;Hsu CW;Chan SP;Yen PS;Su MP;Li JC;Li HH;Cheng L;Tang CK;Ko SH;Tsai HK;Tsai ZT;Akbari OS;Failloux AB;Chen CH

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登革热病毒(DENV)流行的地区迅速扩大,部分原因是作为疾病媒介的伊蚊物种在全球范围内传播。DENV在蚊子中肠内复制,并传播到蚊子的唾液腺进行放大。因此,阻止病毒感染或在蚊子组织中复制可能是减少DENV向人类传播的可行策略。在这里,我们使用Mariner Mos1转座酶创建了一个埃及伊蚊品系,它表达了能够阻止DENV复制的病毒特异性miRNA发夹。这些微RNA是由血粉诱导的羧肽酶A启动子或多泛素启动子驱动的。转基因蚊子在接受感染血餐7天后,大多数DENV血清型的感染率和病毒滴度都显著降低。这种治疗在感染后第14天也有效,在第二次血餐后进行。在病毒传播试验中,我们发现这些品系的传播率显著降低。这些转基因蚊子有效地沉默了DENV的大部分基因组;这种方法可能被用来控制登革热疫情。
The areas where dengue virus (DENV) is endemic have expanded rapidly, driven in part by the global spread of Aedes species, which act as disease vectors. DENV replicates in the mosquito midgut and is disseminated to the mosquito’s salivary glands for amplification. Thus, blocking virus infection or replication in the tissues of the mosquito may be a viable strategy for reducing the incidence of DENV transmission to humans. Here we used the mariner Mos1 transposase to create an Aedes aegypti line that expresses virus-specific miRNA hairpins capable of blocking DENV replication. These microRNA are driven by the blood-meal-inducible carboxypeptidase A promoter or by the polyubiquitin promoter. The transgenic mosquitoes exhibited significantly lower infection rates and viral titers for most DENV serotypes 7 days after receiving an infectious blood meal. The treatment was also effective at day 14 post infection after a second blood meal had been administered. In viral transmission assay, we found there was significantly reduced transmission in these lines. These transgenic mosquitoes were effective in silencing most of the DENV genome; such an approach may be employed to control a dengue fever epidemic.
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