Antagonism of interferon signaling by fibroblast growth factors promotes viral replication

Abstract: Fibroblast growth factors (FGF s) play key roles in the pathogenesis of different human diseases, but the cross‐talk between FGF s and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGF s 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, FGF 7 or FGF 10 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 FGF s 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: EMBO molecular medicine. - 12, 9 (2020) , e11793, ISSN: 1757-4684

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Maddaluno, Luigi ; Urwyler, Corinne ; Rauschendorfer, Theresa ; Meyer, Michael ; Stefanova, Debora ; Spörri, Roman Andreas ; Wietecha, Mateusz ; Ferrarese, Luca ; Stoycheva, Diana ; Bender, Daniela ; Li, Nick ; Strittmatter, Gerhard Egon Mario ; Nasirujjaman, Khondokar ; Beer, Hans‐Dietmar ; Stäheli, Peter ; Hildt, Eberhard ; Oxenius, Annette ; Werner, Sabine

Further information

• DOI: 10.15252/emmm.201911793
• URN: urn:nbn:de:bsz:25-freidok-1667191
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:48 PM CET