The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type i interferon

Maudry Laurent-Rolle, Juliet Morrison, Ricardo Rajsbaum Gorodezky, Jesica M Levingston Macleod, Giuseppe Pisanelli, Alissa Pham, Juan Ayllon, Lisa Miorin, Carles Martínez-Romero, Benjamin R. Tenoever, Adolfo García-Sastre

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)314-327
Number of pages14
JournalCell Host and Microbe
Volume16
Issue number3
DOIs
StatePublished - Sep 10 2014
Externally publishedYes

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Yellow fever virus
Interferons
Antiviral Agents
STAT2 Transcription Factor
Feline Panleukopenia
Flavivirus Infections
Interferon Type I
Ubiquitin-Protein Ligases
Viral Proteins
Lysine
Tyrosine
Phosphorylation
flavivirus NS5 protein

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type i interferon. / Laurent-Rolle, Maudry; Morrison, Juliet; Rajsbaum Gorodezky, Ricardo; Macleod, Jesica M Levingston; Pisanelli, Giuseppe; Pham, Alissa; Ayllon, Juan; Miorin, Lisa; Martínez-Romero, Carles; Tenoever, Benjamin R.; García-Sastre, Adolfo.

In: Cell Host and Microbe, Vol. 16, No. 3, 10.09.2014, p. 314-327.

Research output: Contribution to journalArticle

Laurent-Rolle, M, Morrison, J, Rajsbaum Gorodezky, R, Macleod, JML, Pisanelli, G, Pham, A, Ayllon, J, Miorin, L, Martínez-Romero, C, Tenoever, BR & García-Sastre, A 2014, 'The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type i interferon', Cell Host and Microbe, vol. 16, no. 3, pp. 314-327. https://doi.org/10.1016/j.chom.2014.07.015
Laurent-Rolle, Maudry ; Morrison, Juliet ; Rajsbaum Gorodezky, Ricardo ; Macleod, Jesica M Levingston ; Pisanelli, Giuseppe ; Pham, Alissa ; Ayllon, Juan ; Miorin, Lisa ; Martínez-Romero, Carles ; Tenoever, Benjamin R. ; García-Sastre, Adolfo. / The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type i interferon. In: Cell Host and Microbe. 2014 ; Vol. 16, No. 3. pp. 314-327.
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