Lumpy skin disease virus LSDV001 protein positively regulates inflammatory response by promoting assembly of the TAK1-TAB2/3 complex

文献类型： 外文期刊

第一作者： Yang, Yu-Lin

作者： Yang, Yu-Lin;Jia, Huai-Jie;Sun, Meng-Yao;Guo, Ai-Min;Xia, Tian;Shu, Hong-Bing;Cao, Li-Bo;Yang, Yu-Lin;Jia, Huai-Jie;Sun, Meng-Yao;Guo, Ai-Min;Xia, Tian;Shu, Hong-Bing;Cao, Li-Bo;Yang, Yu-Lin;Jia, Huai-Jie;Sun, Meng-Yao;Guo, Ai-Min;Xia, Tian;Shu, Hong-Bing;Cao, Li-Bo;Shu, Hong-Bing

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关键词： lumpy skin disease virus; inflammation; pathogenesis; LSDV001; TAK1-TAB2/3

期刊名称：MBIO （ 影响因子：4.7； 五年影响因子：5.5 ）

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年卷期： 2025 年

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收录情况： SCI

摘要： Lumpy skin disease (LSD) is an emerging transboundary viral disease of livestock caused by the lumpy skin disease virus (LSDV), which has caused substantial economic losses and negatively impacted veterinary public health. The underlying pathogenic mechanisms remain poorly understood, limiting the effective prevention and control of LSD. Here, we identify LSDV-encoded protein LSDV001 as a positive regulator of IL-1 beta- and TNF alpha-triggered signaling. LSDV001 interacts with TAK1 and TAB2/3 and promotes assembly of the TAK1-TAB2/3 complex. This leads to IKK-dependent activation of the transcription factor NF-kappa B and induction of downstream inflammatory cytokines. LSDV001-deficient virus (LSDV Delta 001) has attenuated the ability to activate NF-kappa B and induce the expression of inflammatory cytokines. Infection with LSDV Delta 001 leads to smaller skin nodules and reduced inflammation compared to wild-type LSDV. Our findings suggest that LSDV001 acts as a key virulence factor of LSDV by promoting excessive inflammatory response upon infection.IMPORTANCELumpy skin disease is a current global concern caused by the lumpy skin disease virus (LSDV), for which there is a lack of safe and efficient vaccines. In this study, we report that LSDV001 protein potentiates IL-1 beta- and TNF alpha-triggered IKK-dependent activation of NF-kappa B and transcription of inflammatory cytokines. Mechanistically, LSDV001 enhances inflammatory response by interacting with TAK1 and TAB2/3 to promote TAK1-TAB2/3 complex formation. We further demonstrate that LSDV001 deficiency attenuates LSDV-triggered inflammatory response and pathogenesis. Our findings identify a new virulence factor and reveal a novel pathogenic mechanism of LSDV by which LSDV001 enhances inflammatory response.

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