Dicer-2 Regulates Resistance and Maintains Homeostasis against Zika Virus Infection in Drosophila.

Dicer-2 Regulates Resistance and Maintains Homeostasis against Zika Virus Infection in Drosophila.
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DOI:
10.4049/jimmunol.1800597
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发表时间:
2018-11-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Eleftherianos I
Eleftherianos I
中科院分区:
其他
文献类型:
--
作者:
Harsh S;Ozakman Y;Kitchen SM;Paquin-Proulx D;Nixon DF;Eleftherianos I

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寨卡病毒(ZIKV)的爆发在一些国家造成了巨大的公共卫生威胁。我们建立了一种体内模型来研究宿主与寨卡病毒在果蝇体内的相互作用。我们已经发现,一种ZIKV毒株在野生型苍蝇中复制而不降低它们的生存能力。我们已经证明,寨卡病毒感染会引发RNA干扰,而突变的Dicer-2会导致寨卡病毒载量增加,并增加对寨卡病毒感染的易感性。利用黄病毒特异性抗体,我们发现ZIKV定位于受感染野生型果蝇的肠道和脂肪体细胞中,并导致它们的体内平衡受到干扰。此外,Dicer-2突变体表现出严重的胰岛素活性降低,这可能导致这些苍蝇的死亡率增加。我们的工作建立了果蝇作为研究宿主- zikv动力学的模型系统的适用性,这有望极大地促进我们对决定这种疾病结果的分子和生理过程的理解。
Zika virus (ZIKV) outbreaks pose a massive public health threat in several countries. We have developed an in vivo model to investigate the host-ZIKV interaction in Drosophila. We have found that a strain of ZIKV replicates in wild-type flies without reducing their survival ability. We have shown that ZIKV infection triggers RNA interference, and that mutating Dicer-2, results in enhanced ZIKV load and increased susceptibility to ZIKV infection. Using a flavivirus-specific antibody, we have found that ZIKV is localized in the gut and fat body cells of the infected wild-type flies and results in their perturbed homeostasis. In addition, Dicer-2 mutants display severely reduced insulin activity, which could contribute towards the increased mortality of these flies. Our work establishes the suitability of Drosophila as the model system to study host-ZIKV dynamics, which is expected to greatly advance our understanding of the molecular and physiological processes that determine the outcome of this disease.
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