The importance of small non-coding RNAs is growing exponentially in modern biology. They have recently emerged as critical regulators of gene expression. Different classes of small RNAs have been defined, and among them micro (mi) RNAs, and small interfering (si) RNAs are the most studied. Viruses interact extensively with the RNA silencing machinery. Thus in plants and insects, they are directly targeted and degraded by Dicer proteins. The situation is more complicated in mammals, where a more sophisticated innate immune response has replaced this antiviral mechanism. Nevertheless, there are interactions between viruses and mammalian RNA silencing pathways, which mainly involve miRNAs. On one hand, miRNAs of cellular origin can regulate viral RNAs, and on the other hand, some viruses have evolved to express their own miRNAs. This project aims at characterizing the full scope of interactions between mammalian viruses and the RNA silencing machinery. Using both RNA and DNA viruses, we will identify cellular miRNAs that have antiviral or proviral properties, and correlate these finding with the changes in cellular miRNA profiles induced by viral infection. We will set apart the mechanisms by which a given cellular miRNA has anti or proviral activity, and the counter methods that viruses could deploy to prevent their targeting. The second part of the project pertains to the study of viral miRNAs, and we will elucidate their roles both during in vitro and in vivo infection; we will also analyze how their expression is regulated. Finally, the last part of the project will consist in deciphering how viruses affect the RNA silencing machinery. This will entitle the characterization of RNA silencing complexes composition and subcellular localization during viral infection.