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- Title
The hepatitis C virus protein NS3 suppresses TNF-α-stimulated activation of NF-κB by targeting LUBAC.
- Authors
Yongzhi Chen; Liang He; Yanan Peng; Xiaodong Shi; Jizheng Chen; Jin Zhong; Xinwen Chen; Genhong Cheng; Hongyu Deng
- Abstract
The transcription factor nuclear factor kB (NF-kB) is crucial for innate immune defense against viral infections, and its activation requires the ubiquitylation of upstream proteins, including the adaptor protein NEMO (NF-κB essential modulator). Many infectious pathogens, including hepatitis C virus (HCV), inhibit NF-κB signaling in host cells, which promotes pathogen survival. Frequently, HCV-infected individuals develop a chronic infection, which suggests that HCV can subvert host antiviral responses. We found that HCV infection and replication inhibited the activation of NF-κB by the inflammatory cytokine tumor necrosis factor-α (TNF-α), which was mediated by the viral protein NS3 and, to a lesser extent, NS5B. NS3 directly interacted with linear ubiquitin chain assembly complex (LUBAC), competed with NEMO for binding to LUBAC, and inhibited the LUBAC-mediated linear ubiquitylation of NEMO and the subsequent activation of NF-κB. Together, our results highlight an immune evasion strategy adopted by HCV to modulate host antiviral responses and enhance virus survival and persistence.
- Subjects
NF-kappa B; VIRUS diseases; UBIQUITINATION; HEPATITIS C virus; TUMOR necrosis factor receptors
- Publication
Science Signaling, 2015, Vol 8, Issue 403, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aab2159