植物和无脊椎动物能在病毒感染中将RNA沉默用作一种保护机制。现在，细胞微RNA也被发现在哺乳动物细胞中有一种抗病毒功能。β-干扰素参与人体细胞中若干种细胞微RNA的调控，其中的8种对于抵抗丙肝病毒上的序列具有活性。此外，细胞微RNA水平的调控还被发现能够显著改变β-干扰素的抗病毒效应，说明它们是哺乳动物先天免疫反应体系的一个功能性构成部分。
原始出处:
Nature 449, 919-922 (18 October 2007) | doi:10.1038/nature06205; Received 26 July 2007; Accepted 29 August 2007
Interferon modulation of cellular microRNAs as an antiviral mechanism
Irene M. Pedersen1, Guofeng Cheng3, Stefan Wieland3, Stefano Volinia4, Carlo M. Croce4, Francis V. Chisari3 & Michael David1,2
Department of Molecular Biology,
Division of Biological Sciences, and,
Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
Division of Experimental Pathology, The Scripps Research Institute, La Jolla, California 92037, USA
Department of Molecular Virology, Immunology & Medical Genetics, Ohio State University, Columbus, Ohio 43210, USA
Correspondence to: Michael David1,2 Correspondence and requests for materials should be addressed to M.D. (Email: midavid@ucsd.edu).
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 elusive1. Here we show that interferon beta (IFN) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFN-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFN-induced miRNAs reproduces the antiviral effects of IFN on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFN against HCV. In addition, we demonstrate that IFN 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 replication2. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.
