Genomic analysis of the modulation of immune signalling by rabies virus P protein

The ability of viruses to evade immunity is critical to disease, presenting targets for vaccine and antivirals development. The principal antiviral response of cells is mediated by interferons, which activate STAT proteins to induce hundreds of genes including antiviral genes. Viruses counter this by expressing ‘interferon-antagonist’ proteins, many of which inhibit STATs. Interferon-antagonists are typically considered to shut down interferon responses, but many interferon-regulated genes have ‘pro-viral’ functions. How viruses coordinate the need to suppress some genes but not others are poorly understood. Using a well-characterised interferon-antagonist, our data indicate that by selectively targeting certain cytokine-activated pathways, interferon-antagonists can inhibit the effects of interferon on specific subsets of IRGs (including antiviral genes) while permitting effects on others (including proviral genes); thus, interferon-antagonists may be defined as selective ‘interferon-modulators.