Flavivirus Antagonism of Type I Interferon Signaling Reveals Prolidase as a Regulator of IFNAR1 Surface Expression
| Autor: | Kirk J. Lubick, Avram D. Walts, Mariko Ishizuka, Alexandra F. Freeman, Conrad B. Addison, Richard Green, Manfred Boehm, Kentaro Yoshii, Michael G. Katze, Sonja M. Best, Erin C. Foster, Abhilash I. Chiramel, Kristin L. McNally, Steven M. Holland, R. Travis Taylor, Seitaro Tsuruda, Mizuki Sakai, Daniel L. Kastner, Angela L. Rasmussen, Shelly J. Robertson, Brett A. Freedman, Antonella Forlino, Elena F. Boer |
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| Jazyk: | angličtina |
| Předmět: |
Dipeptidases
Cancer Research viruses Receptor Interferon alpha-beta Viral Nonstructural Proteins Microbiology Article Virus Encephalitis Viruses Tick-Borne Immune system Interferon Virology Immunology and Microbiology(all) medicine Humans Molecular Biology Prolidase deficiency biology PEPD Fibroblasts biology.organism_classification medicine.disease Molecular biology Cell biology Flavivirus Host-Pathogen Interactions Interferon Type I Parasitology Signal transduction West Nile virus Interferon type I Protein Binding Signal Transduction medicine.drug |
| Zdroj: | Cell Host & Microbe. (1):61-74 |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2015.06.007 |
| Popis: | SummaryType I interferon (IFN-α/β or IFN-I) signals through two receptor subunits, IFNAR1 and IFNAR2, to orchestrate sterile and infectious immunity. Cellular pathways that regulate IFNAR1 are often targeted by viruses to suppress the antiviral effects of IFN-I. Here we report that encephalitic flaviviruses, including tick-borne encephalitis virus and West Nile virus, antagonize IFN-I signaling by inhibiting IFNAR1 surface expression. Loss of IFNAR1 was associated with binding of the viral IFN-I antagonist, NS5, to prolidase (PEPD), a cellular dipeptidase implicated in primary immune deficiencies in humans. Prolidase was required for IFNAR1 maturation and accumulation, activation of IFNβ-stimulated gene induction, and IFN-I-dependent viral control. Human fibroblasts derived from patients with genetic prolidase deficiency exhibited decreased IFNAR1 surface expression and reduced IFNβ-stimulated signaling. Thus, by understanding flavivirus IFN-I antagonism, prolidase is revealed as a central regulator of IFN-I responses. |
| Databáze: | OpenAIRE |
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