The interferon (IFN) response protects cells from invading viral pathogens by transcriptionally inducing the expression of interferon-stimulated genes (ISGs). Only a handful of these ISGs have been well characterized, mainly by artificial gain-of-function screening approaches. We developed an original library of 1156 siRNAs targeting around 386 individual curated human ISGs (46% new) for loss-of-function screening. We have already identified poorly-characterized ISGs that modulate the replication of Zika virus, an emerging RNA virus that belongs to the flaviviridae family.
We propose to use the same approach to identify ISGs that modulate infection of Hepatitis C virus (HCV), which also belongs to the flaviviridae family. Our long-term goal is to perform an in-depth characterization of the mode of action of a set of IFN effectors that exhibit either HCV-specific or pan-flaviviridae modulatory activities. Our work will increase our fundamental knowledge of antiviral response against members of the flaviviridae family. Furthermore, taking advantage of some of these naturally occurring pan-viral inhibitors may be an effective strategy in the development of novel drugs that activate, amplify or mimic their action.