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 , 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226784 | PMC |
| http://dx.doi.org/10.3390/cells9040899 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interlinking pathways: a narrative review on the role of IL-6 in cancer and atherosclerosis.
Cardiovasc Diagn Ther
December 2024
Department of Radiology, University of Cagliari, Cagliari, Italy.
Background And Objective: Interleukin-6 (IL-6) plays multifaceted roles in cancer and atherosclerosis. Initially recognized for its role in immune response and inflammation, IL-6 promotes tumor progression via the JAK-STAT and MAP kinase pathways and is associated with poor cancer prognoses. In atherosclerosis, IL-6 contributes to endothelial dysfunction and plaque formation.
View Article and Find Full Text PDFChinese herbal formula Regan Saibisitan alleviates airway inflammation of chronic bronchitis via inhibiting the JAK2/STAT3 pathway.
J Ethnopharmacol
January 2025
Pharmacy School, Shihezi University, Xinjiang, 832000, China; Xinjiang Key Laboratory of Uygur Medicine, Xinjiang Institute of Materia Medica, Xinjiang, 830000, China. Electronic address:
Ethnopharmacological Relevance: Regan Saibisitan (RGS) is a classic prescription used to treat cough, pneumonia, and other respiratory infections in Uygur medicine. It is a granule composed of 12 kinds of medicinal materials. However, the mechanism by which RGS regulates lung disease remains unclear.
View Article and Find Full Text PDFImpact of p. Gingivalis-induced chronic apical periodontitis on systemic iron homeostasis via the hepatic IL-6/STAT3/Hepcidin signaling pathway.
Int Immunopharmacol
January 2025
State Key Laboratory of Oral Diseases & National Center of Stomatology & National Clinical Research Center for Oral Diseases & Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:
Background And Aims: Chronic apical periodontitis (CAP), an inflammatory disease of the oral cavity caused by bacterial infections with Porphyromonas gingivalis (P. gingivalis) as a key pathogen, has been associated with systemic effects, potentially influencing distant organs including liver. The liver plays a key role in iron metabolism and immunity by hepcidin.
View Article and Find Full Text PDFThe Ability of SOCS1 to Cross-Regulate GM-CSF Signaling is Dose Dependent.
J Interferon Cytokine Res
January 2025
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator of interferon (IFN), interleukin (IL)12, and IL-2 family cytokine signaling through inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. To investigate the temporal induction of SOCS1 in response to cytokine in live cells and its selective regulation of signaling pathways, we generated a mouse expressing a Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control of the endogenous promoter. Homozygous Halo-SOCS1 mice () were viable with minor T cell abnormalities, most likely due to enhanced Halo-SOCS1 expression in thymocytes compared with the untagged protein.
View Article and Find Full Text PDFmiRNA Expression Profile in Primary Limbal Epithelial Cells of Aniridia Patients.
Invest Ophthalmol Vis Sci
January 2025
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Homburg/Saar, Germany, Saarland University, Homburg/Saar, Germany.
Purpose: This study evaluates the microRNA (miRNA) expression profile in primary limbal epithelial cells (pLECs) of patients with aniridia.
Methods: Primary human LECs were sampled and isolated from 10 patients with aniridia and 10 healthy donors. The miRNA profile was analyzed using miRNA microarrays.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!