Collaborative project with Nicolas Manel (Institut Curie)
The interferon (IFN) response protects cells from invading viral pathogens by transcriptionally inducing the expression of interferon-stimulated genes (ISGs). Replication of viral vaccine vectors is also attenuated by IFN, which may limit their immunogenicity. 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. We will perform an in-depth characterization of the mode of action of these ISGs using virological and immunological approaches. We will also identify ISGs that modulate infection of Modified Vaccinia Ankara, a promising immunogenic vaccine vector, and study the underlying mechanism. Our consortium will increase our fundamental knowledge of IFN responses and help identify new targets for antivirals and vaccine improvements.