Flavivirus Nonstructural Protein NS5 Dysregulates HSP90 to Broadly Inhibit JAK/STAT Signaling
| Autor: | Elyse C. Dewey-Verstelle, Marian R. Fairgrieve, Frank Soveg, Emily A. Hemann, Jennifer E. Stencel-Baerenwald, Michael Gale, Ram Savan, Lauren D. Hatfield, Adriana Forero, Justin A Roby, Amy Y. Lu, Brian C. Keller, Alexander Shapiro, Katharina Esser-Nobis, Johannes Schwerk |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
NS5 Viral nonstructural protein medicine.medical_treatment viruses virus–host interactions Viral Nonstructural Proteins Transfection stat Article immune response Cell Line 03 medical and health sciences 0302 clinical medicine flavivirus Interferon medicine cytokine Animals Humans HSP90 HSP90 Heat-Shock Proteins lcsh:QH301-705.5 biology Zika Virus Infection JAK-STAT signaling pathway virus diseases General Medicine Zika Virus biology.organism_classification Virology JAK/STAT Flavivirus 030104 developmental biology Cytokine lcsh:Biology (General) STAT protein anti-viral signaling Zika virus Janus kinase West Nile virus 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Cells, Vol 9, Iss 899, p 899 (2020) Cells Volume 9 Issue 4 |
| ISSN: | 2073-4409 |
| Popis: | Pathogenic flaviviruses antagonize host cell Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling downstream of interferons &alpha /&beta Here, we show that flaviviruses inhibit JAK/STAT signaling induced by a wide range of cytokines beyond interferon, including interleukins. This broad inhibition was mapped to viral nonstructural protein 5 (NS5) binding to cellular heat shock protein 90 (HSP90), resulting in reduced Janus kinase&ndash HSP90 interaction and thus destabilization of unchaperoned JAKs (and other kinase clients) of HSP90 during infection by Zika virus, West Nile virus, and Japanese encephalitis virus. Our studies implicate viral dysregulation of HSP90 and the JAK/STAT pathway as a critical determinant of cytokine signaling control during flavivirus infection. |
| Databáze: | OpenAIRE |
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