Open AccessOptineurin Regulates the Interferon Response in a Cell Cycle-Dependent Manner
Author(s) -
Pierre Génin,
Frédérique Cuvelier,
Sandrine Lambin,
Josina Filipe,
Elodie Autrusseau,
C Laurent,
Emmanuel Laplantine,
Robert Weil
Publication year - 2015
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1004877
Subject(s) - irf3 , optineurin , interferon regulatory factors , tank binding kinase 1 , microbiology and biotechnology , innate immune system , interferon , transcription factor , biology , signal transduction , phosphorylation , protein kinase a , immune system , autophagy , virology , immunology , gene , genetics , cyclin dependent kinase 2 , apoptosis
Viral invasion into a host is initially recognized by the innate immune system, mainly through activation of the intracellular cytosolic signaling pathway and coordinated activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB) transcription factors that promote type I interferon gene induction. The TANK-binding Kinase 1 (TBK1) phosphorylates and activates IRF3. Here, we show that Optineurin (Optn) dampens the antiviral innate immune response by targeting the deubiquitinating enzyme CYLD to TBK1 in order to inhibit its enzymatic activity. Importantly, we found that this regulatory mechanism is abolished at the G2/M phase as a consequence of the nuclear translocation of CYLD and Optn. As a result, we observed, at this cell division stage, an increased activity and phosphorylation of TBK1 that lead to its relocalization to mitochondria and to enhanced interferon production, suggesting that this process, which relies on Optn function, might be of major importance to mount a preventive antiviral response during mitosis.