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Chisari FV 《Nature》2005,436(7053):930-932
The human suffering exacted by the hepatitis C virus is enormous. Hundreds of thousands of people die each year from liver failure and cancer caused by this infection. There is no vaccine, and the available antiviral drugs are toxic, expensive and only partly effective. Progress has been hindered by the absence of cell culture and small-animal models of the infection. Nonetheless, recent advances have yielded several promising new antiviral drugs and enhanced the prospects of developing a vaccine. The recent development of a robust in vitro hepatitis C virus infection system will aid this search. 相似文献
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RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in the defence against viral infection in mammalian organisms has thus far remained elusive. Here we show that interferon beta (IFNbeta) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFNbeta-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFNbeta-induced miRNAs reproduces the antiviral effects of IFNbeta on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFNbeta against HCV. In addition, we demonstrate that IFNbeta treatment leads to a significant reduction in the expression of the liver-specific miR-122, an miRNA that has been previously shown to be essential for HCV replication. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections. 相似文献
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