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PMID:25211074
| Citation |
Laurent-Rolle, M, Morrison, J, Rajsbaum, R, Macleod, JML, Pisanelli, G, Pham, A, Ayllon, J, Miorin, L, Martinez, C, tenOever, BR and García-Sastre, A (2014) The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type I interferon. Cell Host Microbe 16:314-327 |
|---|---|
| Abstract |
To successfully establish infection, flaviviruses have to overcome the antiviral state induced by type I interferon (IFN-I). The nonstructural NS5 proteins of several flaviviruses antagonize IFN-I signaling. Here we show that yellow fever virus (YFV) inhibits IFN-I signaling through a unique mechanism that involves binding of YFV NS5 to the IFN-activated transcription factor STAT2 only in cells that have been stimulated with IFN-I. This NS5-STAT2 interaction requires IFN-I-induced tyrosine phosphorylation of STAT1 and the K63-linked polyubiquitination at a lysine in the N-terminal region of YFV NS5. We identified TRIM23 as the E3 ligase that interacts with and polyubiquitinates YFV NS5 to promote its binding to STAT2 and trigger IFN-I signaling inhibition. Our results demonstrate the importance of YFV NS5 in overcoming the antiviral action of IFN-I and offer a unique example of a viral protein that is activated by the same host pathway that it inhibits. |
| Links |
PubMed PMC4176702 Online version:10.1016/j.chom.2014.07.015 |
| Keywords |
Amino Acid Motifs; Animals; Cell Line; GTP-Binding Proteins/genetics; GTP-Binding Proteins/metabolism; Host-Pathogen Interactions; Humans; Interferon-beta/metabolism; Phosphorylation; Protein Binding; STAT1 Transcription Factor/chemistry; STAT1 Transcription Factor/genetics; STAT1 Transcription Factor/metabolism; STAT2 Transcription Factor/genetics; STAT2 Transcription Factor/metabolism; Signal Transduction; Viral Nonstructural Proteins/antagonists & inhibitors; Viral Nonstructural Proteins/chemistry; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/metabolism; Yellow Fever/genetics; Yellow Fever/metabolism; Yellow Fever/virology; Yellow fever virus/genetics; Yellow fever virus/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0039502: suppression by virus of host type I interferon-mediated signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
Notes
See also
References
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