RRC ID 67921
著者 Fliss PM, Jowers TP, Brinkmann MM, Holstermann B, Mack C, Dickinson P, Hohenberg H, Ghazal P, Brune W.
タイトル Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade.
ジャーナル PLoS Pathog
Abstract The early host response to viral infections involves transient activation of pattern recognition receptors leading to an induction of inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Subsequent activation of cytokine receptors in an autocrine and paracrine manner results in an inflammatory cascade. The precise mechanisms by which viruses avert an inflammatory cascade are incompletely understood. Nuclear factor (NF)-κB is a central regulator of the inflammatory signaling cascade that is controlled by inhibitor of NF-κB (IκB) proteins and the IκB kinase (IKK) complex. In this study we show that murine cytomegalovirus inhibits the inflammatory cascade by blocking Toll-like receptor (TLR) and IL-1 receptor-dependent NF-κB activation. Inhibition occurs through an interaction of the viral M45 protein with the NF-κB essential modulator (NEMO), the regulatory subunit of the IKK complex. M45 induces proteasome-independent degradation of NEMO by targeting NEMO to autophagosomes for subsequent degradation in lysosomes. We propose that the selective and irreversible degradation of a central regulatory protein by autophagy represents a new viral strategy to dampen the inflammatory response.
巻・号 8(2)
ページ e1002517
公開日 2012-2-1
DOI 10.1371/journal.ppat.1002517
PII PPATHOGENS-D-11-01625
PMID 22319449
PMC PMC3271075
MeSH Animals Autophagy I-kappa B Kinase / metabolism* Inflammation Interleukin-1beta / metabolism Intracellular Signaling Peptides and Proteins / metabolism* Mice Muromegalovirus / metabolism* NF-kappa B / antagonists & inhibitors* NF-kappa B / metabolism NIH 3T3 Cells Phagosomes / immunology* Receptors, Interleukin-1 / antagonists & inhibitors Receptors, Interleukin-1 / immunology Receptors, Interleukin-1 / metabolism Signal Transduction / immunology Toll-Like Receptors / antagonists & inhibitors Toll-Like Receptors / immunology Toll-Like Receptors / metabolism Tumor Necrosis Factor-alpha / metabolism
IF 6.218
リソース情報
ヒト・動物細胞 Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711)