Flavivirus Nonstructural Protein NS5 Dysregulates HSP90 to Broadly Inhibit JAK/STAT Signaling
Year: 2020
Type: article
Abstract: Pathogenic flaviviruses antagonize host cell Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling downstream of interferons α/β. 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–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.
Source: Cells
DOI: 10.3390/cells9040899
Institutions: University of Washington, The Ohio State University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Awards: Mechanisms of hepatic innate immune activation by HCV, Diseases of Public Health Importance Training Grant, Innate Immune Regulation of Zika Virus Infection, Systems Immunogenetics of Biodefense and Emerging Pathogens in the Collaborative Cross, Innate Immune Control of West Nile Virus, Training in Cellular and Molecular Biology, Regulation of dendritic cell function and protective respiratory immunity by interferon-lambda, G7970403308, JAK-STAT Control of Zika Virus-Induced Fetal Injury, G9000141081
OpenAlex ID: W3015494074