Cytomegalovirus microRNAs facilitate persistent virus infection in salivary glands.
Cytomegalovirus microRNAs facilitate persistent virus infection in salivary glands.
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DOI：
10.1371/journal.ppat.1001150
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发表时间：
2010-10-14
期刊：
影响因子：
6.7
通讯作者：
Pfeffer S
中科院分区：
文献类型：
--
作者：
Dölken L;Krmpotic A;Kothe S;Tuddenham L;Tanguy M;Marcinowski L;Ruzsics Z;Elefant N;Altuvia Y;Margalit H;Koszinowski UH;Jonjic S;Pfeffer S
Micro(Mi)RNAs是一种小的非编码RNAs，它通过翻译抑制和调节靶标RNA的稳定性来调节靶标信使RNAs的表达。最近，一些病毒，特别是疱疹病毒家族的病毒，已经被证明表达它们自己的miRNAs来控制病毒和细胞转录。虽然病毒miRNAs的一些靶点已知，但它们在生理相关感染中的功能仍有待阐明。因此，到目前为止还没有描述病毒miRNA敲除突变体的体内表型。在这里，我们报告了体内首个miRNA敲除病毒的功能表型。在亚急性感染缺乏两个病毒miRNAs的突变小鼠巨细胞病毒期间，唾液腺中的病毒产量选择性地减少，唾液腺是病毒持续和水平传播所必需的器官。这种表型取决于几个参数，包括病毒载量和小鼠遗传背景，并被自然杀伤(NK)和CD4+T细胞联合但不是单一耗尽所消除。总而言之，我们的结果指向了一种基于miRNA的免疫逃避机制，这对病毒的长期持久性很重要。最近发现的病毒来源的miRNAs极大地改变了我们对病毒与宿主相互作用的看法。病毒miRNAs已被证明可以调节细胞和病毒来源的基因，为病毒创造有利的环境。然而，病毒编码的miRNAs在感染宿主过程中的真正重要性仍然难以捉摸。在这篇手稿中，我们报道了小鼠巨细胞病毒miRNA敲除突变体在体内的第一个功能表型。我们发现，突变病毒在受感染小鼠的唾液腺中特异性减弱，唾液腺是病毒长期存活和宿主到宿主传播所必需的器官。有趣的是，这种衰减揭示了研究中的小鼠对遗传背景的显著依赖。只有自然杀伤细胞和T细胞的联合去除才能消除这种表型。这些结果表明，通过调节免疫系统，病毒miRNAs可能在有效持续感染中发挥重要作用。
Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence. The recent discovery of miRNAs of viral origin has dramatically changed our view on virus-host interaction. Viral miRNAs have been shown to regulate genes of both cellular and viral origin, contributing to a favorable environment for the virus. However, the real importance of virus-encoded miRNAs during infection of their hosts remains elusive. In this manuscript, we report on the first functional phenotype of a miRNA knock-out mutant of the mouse cytomegalovirus in vivo. We show that the mutant virus is attenuated specifically in the salivary glands of infected mice, an organ essential for long-term persistence of the virus and host-to-host spread. Interestingly, this attenuation revealed a striking dependence on genetic background of the mice under study. Only combined depletion of natural killer and T cells abolished the phenotype. These results indicate that, by regulating the immune system, viral miRNAs may play an important role in an efficient persistent infection.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
5.4
作者：
REDDEHASE, MJ;WEILAND, F;KOSZINOWSKI, UH
通讯作者：
KOSZINOWSKI, UH
影响因子：
--
作者：
Brune, W;Hengel, H;Koszinowski, U H
通讯作者：
Koszinowski, U H
影响因子：
4.4
作者：
Abel, S;Hundhausen, C;Ludwig, A
通讯作者：
Ludwig, A
DOI：
10.1084/jem.169.4.1199
发表时间：
1989-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jonjić S;Mutter W;Weiland F;Reddehase MJ;Koszinowski UH
通讯作者：
Koszinowski UH