The interferon-stimulated genes: targets of direct signaling by interferons, double-stranded RNA, and viruses.

The interferon system plays a profound role in determining the outcome of viral infection in mammals. Viruses induce the synthesis of interferon, which, in turn, blocks virus replication by inducing the expression of antiviral proteins encoded by interferon-stimulated genes. It is not widely appreciated that without the participation of interferon, many of the same genes can also be induced by a variety of virus-related agents, such as double-stranded RNA and viral proteins. In this chapter, we discuss different signaling pathways, activated by these agents, that lead to the induction of partially overlapping sets of genes, including the interferon-stimulated genes. We also review the biochemical and cellular properties of the protein products of a selected number of these genes including ISG56, ISG54, and ISG15.