数字农科院2.0

Lumpy skin disease virus LSDV087 positively regulates innate immune response by promoting oligomerization of MITA/STING

文献类型： 外文期刊

作者： Li, Zhen-Zhen;Yang, Yu-Lin;Sun, Meng-Yao;Shu, Hong-Bing;Cao, Li-Bo

作者机构：

关键词： lumpy skin disease virus;LSDV087;cGAS;MITA/STING;innate immunity

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Lumpy skin disease (LSD), caused by the lumpy skin disease virus (LSDV), is a contagious disease in cattle that poses a major threat to the global cattle industry. The functions of most LSDV-encoded proteins remain poorly characterized, particularly regarding their roles in regulating innate immunity. In this study, we show that the LSDV-encoded protein LSDV087 positively regulates innate immune response independently of its decapping enzymatic activity. LSDV087 interacts with the adaptor protein MITA (also called STING) in the innate immune pathway, inhibits its degradation by reducing K48-linked polyubiquitination, and promotes its oligomerization and subsequent activation of downstream signaling events, leading to enhanced innate immune response. Consistently, LSDV087-deficient virus (LSDV triangle 087) exhibits an attenuated ability to activate cGAS-MITA-mediated innate immune response. Collectively, our study reveals regulatory mechanisms of LSDV-triggered innate immune response and points to the possibility of targeting LSDV087 for rational design of live-attenuated LSDV vaccines.IMPORTANCELumpy skin disease virus (LSDV), which causes a contagious disease in cattle, poses a significant threat to the global cattle industry. Despite its impact, the functions of most LSDV-encoded proteins remain poorly understood. In this study, we report that LSDV087 plays dual roles in both promoting the cGAS-MITA-mediated innate immune response and downregulating host gene transcription. LSDV087 interacts with the adaptor protein MITA in the innate immune pathway, inhibits its degradation by reducing K48-linked polyubiquitination, and promotes its oligomerization, leading to the subsequent activation of downstream signaling events and an enhanced innate immune response. Additionally, as an immediate-early protein, LSDV087 functions as a decapping enzyme, preferentially targeting host transcripts with multiple exons to facilitate viral replication. This dual functionality underscores the complex interplay between LSDV immune evasion strategies and host defense mechanisms and may inform the rational design of live-attenuated LSDV vaccines.

分类号：

  • 相关文献

[1]The Cgas-Sting Signaling Pathway Is R.equired For The Innate I mmune Response Against Ectromelia Virus. Cheng, WY,He, XB,Jia, HJ,Chen, GH,Jin, QW,Long, ZL,Jing, ZZ. 2018

[2]Bacteriophages inhibit and evade cGAS-like immune function in bacteria. Huiting E.,Cao X.,Ren J.,Athukoralage J.S.,Luo Z.,Silas S.,An N.,Carion H.,Zhou Y.,Fraser J.S.,Feng Y.,Bondy-Denomy J.. 2023

[3]猪环鸟苷酸-腺苷酸合成酶cGAS基因的原核表达及其表达产物的生物活性分析. 龙朝琳,何小兵,陈国华,贾怀杰,王国蒨,房永祥,景志忠. 2019

[4]cGAS-STING 信号通路：免疫监视的重要机制. 周萍萍,,王涛,,孙元,,仇华吉. 2022

[5]cGAS-STING信号通路:免疫监视的重要机制. 周萍萍,王涛,孙元,仇华吉. 2021

[6]African swine fever virus E120R protein inhibits interferon beta production by interacting with IRF3 to block its activation. Huisheng Liu,Zixiang Zhu,Tao Feng,Zhao Ma,Qiao Xue,Panxue Wu,Pan Li,Shasha Li,Fan Yang,Weijun Cao,Zhaoning Xue,Hongjun Chen,Xiangtao Liu,Haixue Zheng. 2021

[7]The African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKε. Jia Luo,Jiajia Zhang,Jinghua Ni,Sen Jiang,Nengwen Xia,Yiwen Guo,Qi Shao,Qi Cao,Wanglong Zheng,Nanhua Chen,Quan Zhang,Hongjun Chen,Qing Chen,Hongfei Zhu,François Meurens,Jianzhong Zhu. 2022

[8]cGAS Restricts PRRSV Replication by Sensing the mtDNA to Increase the cGAMP Activity. Xiao Na Liu,Li Wei Li,Fei Gao,Yi Feng Jiang,Wan Zhe Yuan,Guo Xin Li,Ling Xue Yu,Yan Jun Zhou,Guang Zhi Tong,Kuan Zhao. 2022

[9]Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA. Sunnie M. Yoh,João I. Mamede,Derrick Lau,Narae Ahn,Maria T. Sánchez-Aparicio,Joshua Temple,Andrew Tuckwell,Nina V. Fuchs,Gianguido C. Cianci,Laura Riva,Heather Curry,Xin Yin,Stéphanie Gambut,Lacy M. Simons,Judd F. Hultquist,Renate König,Yo. 2022

[10]ArfGAP2 promotes STING proton channel activity, cytokine transit, and autoinflammation. Subhajit Poddar,Samuel D. Chauvin,Christopher H. Archer,Wei Qian,Jean A. Castillo-Badillo,Xin Yin,W. Miguel Disbennett,Cathrine A. Miner,Joe A. Holley,Teresa V. Naismith,W. Alexander Stinson,Xiaochao Wei,Yue Ning,Jiayuan Fu,Trini A. Ochoa,Nehalee Surve,Shivam A. Zaver,Kimberly A. Wodzanowski,Katherine R. Balka,Rajan Venkatraman,Canyu Liu,Kelly Rome,Will Bailis,Yoko Shiba,Sara Cherry,Sunny Shin,Clay F. Semenkovich,Dominic De Nardo,Sunnie Yoh,Elisha D.O. Roberson,Sumit K. Chanda,David J. Kast,Jonathan J. Miner. 2025

[11]Understanding the research advances on lumpy skin disease: A comprehensive literature review of experimental evidence. Zhengji Liang,Kaishen Yao,Shasha Wang,Juanbin Yin,Xiaoqin Ma,Xiangping Yin,Xiangwei Wang,Yuefeng Sun. 2022

[12]The comparative study revealed that the hTERT-CSF cell line was the most susceptible cell to the Lumpy skin disease virus infection among eleven cells. Chunling Ma,Shanhui Ren,Tadele Berihun Afera,Xue Yang,Yugang Lin,Xiaohong Gao,Fangping Wang,Xusheng Qiu,Xiangwei Wang,Xiangping Yin,Yuefeng Sun,Xuerui Wan,Hao tai Chen. 2023

[13]Identification of the murine osteoblastic cell MC3T3-E1 as a permissive cell line in response to lumpy skin disease virus. Ting You,Meng Wang,Hongqiang Zhang,Xiangwei Wang,Xiaolong Gao,Xiangping Yin,Yuefeng Sun,Guirong Wang,Hao tai Chen,Shanhui Ren. 2024

[14]Platform establishment of the Cre-loxP recombination system for genetic manipulation of the Lumpy skin disease virus. Shanhui Ren,Yuzhe Zhang,Xiaolong Gao,Xiangwei Wang,Lina Tong,Shasha Wang,Yuefeng Sun,Xiangping Yin,Haotai Chen. 2024

[15]Phylogenetic and pathogenic characterization of lumpy skin disease virus circulating in China. Shanhui Ren,Haotai Chen,Lvfeng Yuan,Xue Yang,Tadele Berihun Afera,Zaib Ur Rehman,Huibao Wang,Xiangwei Wang,Chunling Ma,Yuguang Lin,Xusheng Qiu,Xiangping Yin,Yuefeng Sun. 2023

[16]Lumpy Skin Disease Virus Infection Activates Autophagy and Endoplasmic Reticulum Stress-Related Cell Apoptosis in Primary Bovine Embryonic Fibroblast Cells. Jinlong Tan,Yinju Liu,Weike Li,Yongzhi Zhang,Guohua Chen,Yongxiang Fang,Xiaobing He,Zhizhong Jing. 2023

[17]Lumpy skin disease virus LSDV001 protein positively regulates inflammatory response by promoting assembly of the TAK1-TAB2/3 complex. Yang, Yu-Lin,Jia, Huai-Jie,Sun, Meng-Yao,Guo, Ai-Min,Xia, Tian,Shu, Hong-Bing,Cao, Li-Bo. 2025

[18]Lumpy Skin Disease Virus ORF137 Protein Inhibits Type I Interferon Production by Interacting with and Decreasing the Phosphorylation of IRF3. Qunhua Ke,Kaishen Yao,Min Qu,Zhengji Liang,Miaomiao Li,Xiangwei Wang,Xiangping Yin,Yuefeng Sun. 2025

[19]Construction and biological characteristics analysis of a gene-deleted recombinant virus strain of LSDV-ORF151. Jiaqi Li,Qunhua Ke,Weitao Huang,Shanhui Ren,Miaomiao Li,Kaishen Yao,Xiaoqin Ma,Yuefeng Sun,Xiangping Yin. 2025

[20]Targeting of the cellular ATM rather than ATR kinase exhibits therapeutic potential during the lumpy skin disease virus infection in vivo and in vitro. Shanhui Ren,Haotai Chen,Shasha Wang,Zaib Ur Rehman,Xiaolong Gao,Xue Yang,Xiangwei Wang,Xiangping Yin,Jianlin Han,Yuefeng Sun. 2025

作者其他论文 更多>>