摘要: The transcription factor nuclear factor kB (NF-kappa B) is crucial for innate immune defense against viral infections, and its activation requires the ubiquitylation of upstream proteins, including the adaptor protein NEMO (NF-kappa B essential modulator). Many infectious pathogens, including hepatitis C virus (HCV), inhibit NF-kappa B 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-kappa B by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), 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-kappa B. Together, our results highlight an immune evasion strategy adopted by HCV to modulate host antiviral responses and enhance virus survival and persistence.
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期刊:
SCIENCE SIGNALING
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分类:
生物学
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生物物理学
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生物物理、生物化学与分子生物学
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引用:
ChinaXiv:201605.01497
(或此版本
ChinaXiv:201605.01497V1)
DOI:10.12074/201605.01497V1
CSTR:32003.36.ChinaXiv.201605.01497.V1
- 推荐引用方式:
Chen, Yongzhi,He, Liang,Peng, Yanan,Shi, Xiaodong,Cheng, Genhong,Deng, Hongyu,Chen, Yongzhi,He, Liang,Peng, Yanan,Chen, Jizheng,Chen, Xinwen,Zhong, Jin,Cheng, Genhong,.(2016).The hepatitis C virus protein NS3 suppresses TNF-alpha-stimulated activation of NF-kappa B by targeting LUBAC.中国生物工程预印本出版平台.[ChinaXiv:201605.01497]
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