Antagonism of interferon signaling by fibroblast growth factors promotes viral replication

Autor: Maddaluno, Luigi, Urwyler, Corinne, Rauschendorfer, Theresa, Meyer, Michael, Stefanova, Debora, Spörri, Roman, Wietecha, Mateusz, Ferrarese, Luca, Stoycheva, Diana, Bender, Daniela, Li, Nick, Strittmatter, Gerhard, Nasirujjaman, Khondokar, Beer, Hans-Dietmar, Staeheli, Peter, Hildt, Eberhard, Oxenius, Annette, Werner, Sabine
Přispěvatelé: University of Zurich, Maddaluno, Luigi, Werner, Sabine
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EMBO Molecular Medicine, 12 (9)
EMBO Molecular Medicine
EMBO Molecular Medicine, Vol 12, Iss 9, Pp n/a-n/a (2020)
EMBO molecular medicine, 12(9):e11793
ISSN: 1757-4676
1757-4684
Popis: 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.
EMBO Molecular Medicine, 12 (9)
ISSN:1757-4676
ISSN:1757-4684
Databáze: OpenAIRE
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