Matskevich Alexey A, Moelling Karin
Institute of Medical Virology, University of Zurich, Gloriastrasse 30/32, CH-8006 Zurich, Switzerland.
J Gen Virol. 2007 Oct;88(Pt 10):2627-2635. doi: 10.1099/vir.0.83103-0.
In mammals the interferon (IFN) system is a central innate antiviral defence mechanism, while the involvement of RNA interference (RNAi) in antiviral response against RNA viruses is uncertain. Here, we tested whether RNAi is involved in the antiviral response in mammalian cells. To investigate the role of RNAi in influenza A virus-infected cells in the absence of IFN, we used Vero cells that lack IFN-alpha and IFN-beta genes. Our results demonstrate that knockdown of a key RNAi component, Dicer, led to a modest increase of virus production and accelerated apoptosis of influenza A virus-infected cells. These effects were much weaker in the presence of IFN. The results also show that in both Vero cells and the IFN-producing alveolar epithelial A549 cell line influenza A virus targets Dicer at mRNA and protein levels. Thus, RNAi is involved in antiviral response, and Dicer is important for protection against influenza A virus infection.
在哺乳动物中,干扰素(IFN)系统是一种核心的先天性抗病毒防御机制,而RNA干扰(RNAi)在针对RNA病毒的抗病毒反应中的作用尚不确定。在此,我们测试了RNAi是否参与哺乳动物细胞的抗病毒反应。为了研究在缺乏干扰素的情况下RNAi在甲型流感病毒感染细胞中的作用,我们使用了缺乏IFN-α和IFN-β基因的Vero细胞。我们的结果表明,关键RNAi组分Dicer的敲低导致病毒产生适度增加,并加速了甲型流感病毒感染细胞的凋亡。在存在干扰素的情况下,这些作用要弱得多。结果还表明,在Vero细胞和产生干扰素的肺泡上皮A549细胞系中,甲型流感病毒在mRNA和蛋白质水平上靶向Dicer。因此,RNAi参与抗病毒反应,并且Dicer对于抵御甲型流感病毒感染很重要。