Wolbachia-mediated resistance to dengue virus infection and death at the cellular level.

Wolbachia-mediated resistance to dengue virus infection and death at the cellular level.
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DOI:
10.1371/journal.pone.0013398
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发表时间:
2010-10-15
期刊:
影响因子:
3.7
通讯作者:
O'Neill SL
O'Neill SL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Frentiu FD;Robinson J;Young PR;McGraw EA;O'Neill SL

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登革热是目前人类最重要的节肢动物传播的病毒性疾病。最近的研究表明,当埃及伊蚊携带内共生细菌沃尔巴克氏菌时,登革热病毒在其主要载体埃及伊蚊中显示出有限的复制。沃尔巴克氏体介导的病毒复制抑制可能会导致虫媒病毒控制的新方法,但其功能和细胞机​​制尚不清楚。使用配对的沃尔巴克氏体感染和未感染的伊蚊衍生细胞系和登革热病毒,我们证实了细胞水平上的病毒抑制现象。尽管沃尔巴克氏体通过减少增殖对细胞造成适应性成本,但它也提供了显着程度的保护,防止病毒引起的死亡。病毒抑制的程度与每个细胞中沃尔巴克氏体的密度有关,高度感染的细胞系表现出几乎完全免受登革热感染的保护,并且与未感染该细菌的细胞系相比,病毒滴度显着降低。我们已经证明,感染沃尔巴克氏体的细胞表现出对登革热病毒复制的抑制,抑制程度与细菌密度有关,并且沃尔巴克氏体感染虽然成本高昂,但在某些情况下将提供健康益处。我们的结果与蚊子和苍蝇的研究结果相似,表明细胞系模型将提供有用且实验上易于处理的模型来研究沃尔巴克氏体介导的病毒保护机制。
Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown. Using paired Wolbachia-infected and uninfected Aedes-derived cell lines and dengue virus, we confirm the phenomenon of viral inhibition at the cellular level. Although Wolbachia imposes a fitness cost to cells via reduced proliferation, it also provides a significant degree of protection from virus-induced mortality. The extent of viral inhibition is related to the density of Wolbachia per cell, with highly infected cell lines showing almost complete protection from dengue infection and dramatically reduced virus titers compared to lines not infected with the bacteria. We have shown that cells infected with Wolbachia display inhibition of dengue virus replication, that the extent of inhibition is related to bacterial density and that Wolbachia infection, although costly, will provide a fitness benefit in some circumstances. Our results parallel findings in mosquitoes and flies, indicating that cell line models will provide useful and experimentally tractable models to study the mechanisms underlying Wolbachia-mediated protection from viruses.
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