Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses.
Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses.
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DOI：
10.1371/journal.pbio.1000586
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发表时间：
2011-01-25
期刊：
影响因子：
9.8
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Félix MA;Ashe A;Piffaretti J;Wu G;Nuez I;Bélicard T;Jiang Y;Zhao G;Franz CJ;Goldstein LD;Sanroman M;Miska EA;Wang D
新的病毒已被发现在野生Causahbditis线虫分离株，现在可以用来探索宿主的抗病毒途径，线虫生态学，和宿主-病原体的共同进化。研究抗病毒免疫和宿主-病原体协同进化的理想模型系统将联合收割机遗传上易于驾驭的小动物和能够自然感染宿主生物体的病毒。C.线虫作为确定宿主-病毒相互作用的模型受到缺乏已知感染线虫的病毒的限制。从C. elegans和C. Briggsae在肠细胞中具有不寻常的形态表型，我们鉴定了两种与已知野田病毒有远亲关系的新型RNA病毒，一种特异性感染C. elegans（奥赛病毒），另一种C. Briggsae（Santeuil病毒）。漂白胚胎治愈了感染的培养物，表明病毒既不能稳定地整合在宿主基因组中，也不能垂直传播。0.2感染的培养物可以感染治愈的动物。感染的动物连续保持病毒感染6个月（150代），表明水平病毒传播的自然周期在实验室培养中被忠实地再现。除了感染天然的C. elegans分离株，奥赛病毒易感染实验室C.与相应的野生型N2株的感染相比，在RNAi中有缺陷的线虫突变体产生更高水平的病毒RNA和感染症状。这些结果证明了RNAi在防御这种病毒中的明确作用。此外，不同野生C.线虫分离株对奥赛病毒感染表现出不同的易感性，从而提供了确定抗病毒基因座的遗传学方法。这一发现建立了一个真正的病毒感染系统，以探索线虫的自然生态，宿主-病原体共同进化，小RNA反应的进化和先天抗病毒机制。线虫C.秀丽线虫是生物学中广泛使用的健壮模式生物。它在宿主-微生物相互作用的研究中也有很大的潜力，因为它可以以高通量的方式系统地敲除几乎每个基因，以检查每个基因在感染中的潜在作用。而C.尽管线虫已经成功地应用于细菌感染的研究，但由于先前没有描述能够在实验室培养中感染任何小杆线虫的病毒，因此仅可能进行有限的抗病毒应答研究。在这里，我们报告的发现，自然病毒感染野生分离的C。elegans及其近缘种C.布里格塞这些新型病毒与ssRNA野田病毒最密切相关，但具有比其他描述的野田病毒更大的基因组，并且清楚地代表了病毒的新分类群。我们能够用这些病毒感染各种实验室线虫菌株。我们发现，突变蠕虫在RNA干扰途径，一种抗病毒系统，已知在许多生物体中运作的缺陷，积累更多的病毒RNA比野生型菌株。这些病毒的发现将为进一步研究C.线虫和其他宿主机制的识别，对抗病毒感染。
Novel viruses have been discovered in wild Caenorahbditis nematode isolates and can now be used to explore host antiviral pathways, nematode ecology, and host-pathogen co-evolution. An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host-viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 µm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (∼50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms. The nematode C. elegans is a robust model organism that is broadly used in biology. It also has great potential for the study of host-microbe interactions, as it is possible to systematically knockout almost every gene in high-throughput fashion to examine the potential role of each gene in infection. While C. elegans has been successfully applied to the study of bacterial infections, only limited studies of antiviral responses have been possible since no virus capable of infecting any Caenorhabditis nematode in laboratory culture has previously been described. Here we report the discovery of natural viruses infecting wild isolates of C. elegans and its relative C. briggsae. These novel viruses are most closely related to the ssRNA nodaviruses, but have larger genomes than other described nodaviruses and clearly represent a new taxon of virus. We were able to use these viruses to infect a variety of laboratory nematode strains. We show that mutant worms defective in the RNA interference pathway, an antiviral system known to operate in a number of organisms, accumulate more viral RNA than wild type strains. The discovery of these viruses will enable further studies of host-virus interactions in C. elegans and the identification of other host mechanisms that counter viral infection.
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影响因子：
56.9
作者：
Li, HW;Li, WX;Ding, SW
通讯作者：
Ding, SW
影响因子：
64.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.0506442103
发表时间：
2006-03-14
影响因子：
11.1
作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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