GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302359/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302359GEOGSEfalseInterferons promote autophagy via the STAT1/STAT5B-SOCS1 axisConcerted activation of the interferon (IFN) system and autophagy upon viral infection is paramount for efficient immune defences. Here, we show that IFN activates autophagy via STAT1/5B heterodimer-mediated upregulation of SOCS1 and contributes to virus-induced autophagy. Our data demonstrate that autophagic flux activation by type I and II IFNs peaks at 24 h post treatment, whereas type III IFNs induce autophagy with slower kinetics. Mechanistically, IFN-mediated autophagy induction is dependent on JAK1-3 and both STAT1 as well as STAT5B. We show that STAT1 and STAT5B form heterodimers and co-localize following IFN treatment. Transcriptome analyses revealed that SOCS1 is induced in a STAT5B-dependent manner, and depletion of SOCS1 prevented IFN-induced autophagy. Finally, pharmacological inhibition of STAT5B or scavenging of IFN diminishes autophagosome levels upon infection with Sendai, respiratory syncytial, measles and influenza A viruses. Taken together, our data indicate that the IFN system and autophagy are connected via the STAT1/STAT5B-SOCS1 axis and that this axis is required for concerted activation of both systems during viral infections. Targeting of this signalling axis may allow to boost autophagy against viral infections.2026/07/01GSE302359GSM9102628GSM9102627GSM9102638GSM9102629GSM9102635GSM9102634GSM9102637GSM9102636GSM9102631GSM9102630GSM9102633GSM910263230173302359Homo sapiens