Antagonism of interferon signaling by fibroblast growth factors promotes viral replication
Abstract
Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross‐talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FGF receptor signaling in keratinocytes promoted the expression of interferon‐stimulated genes (ISG) and proteins in vitro and in vivo. Conversely, FGF7 or FGF10 treatment of keratinocytes suppressed ISG expression under homeostatic conditions and in response to IFN or poly(I:C) treatment. FGF‐mediated ISG suppression was independent of IFN receptors, occurred at the transcriptional level, and required FGF receptor kinase and proteasomal activity. It is not restricted to keratinocytes and functionally relevant, since FGFs promoted the replication of herpes simplex virus I (HSV‐1), lymphocytic choriomeningitis virus, and Zika virus. Most importantly, inhibition of FGFR signaling blocked HSV‐1 replication in cultured human keratinocytes and in mice. These results suggest the use of FGFR kinase inhibitors for the treatment of viral infections. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000431280Publication status
publishedExternal links
Journal / series
EMBO Molecular MedicineVolume
Pages / Article No.
Publisher
WileySubject
Fibroblast growth factor; FGF receptor; Herpes simplex virus; Interferon; Zika virusOrganisational unit
03520 - Werner, Sabine / Werner, Sabine
03625 - Oxenius, Annette / Oxenius, Annette
Funding
169204 - Role of cytokines and environmental cues in wound repair and inflammatory skin disease (SNF)
189364 - Role of cytokines and environmental cues in inflammatory skin disease (SNF)
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