Research ArticleImmunology

The hepatitis C virus protein NS3 suppresses TNF-α–stimulated activation of NF-κB by targeting LUBAC

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Science Signaling  17 Nov 2015:
Vol. 8, Issue 403, pp. ra118
DOI: 10.1126/scisignal.aab2159

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How HCV suppresses NF-κB activation

The inflammatory cytokine TNF-α induces antiviral immune responses by stimulating the transcription factor NF-κB. Patients chronically infected with hepatitis C virus (HCV) have increased serum amounts of TNF-α but ineffective immune responses. Chen et al. found that the HCV protein NS3 blocked TNF-α–stimulated NF-κB activation in a human hepatocyte cell line. Through competitive binding, NS3 blocked the interaction between the adaptor protein NEMO and the multiprotein complex LUBAC, which is required for the ubiquitylation of NEMO and the activation of NF-κB. Given the current lack of a vaccine against HCV, developing therapies that target viral proteins is important for controlling infections.

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