Classical swine fever virus recruits ALIX and ESCRT-III to facilitate viral budding

文献类型： 外文期刊

第一作者： Chen, Jinxia

作者： Chen, Jinxia;Yang, Hanfei;Wan, Mingyue;Cheng, Yan;Bai, Jishan;Li, Yuhang;Chen, Jing;Zhao, Bingqian;Zhou, Bin;Gao, Fei

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关键词： CSFV; budding; ESCRT; ALIX; vesicle transport

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 16 卷 4 期

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收录情况： SCI

摘要： Classical swine fever virus (CSFV) incurs substantial economic losses in the global swine industry due to its persistent emergence and re-emergence across various countries. However, the precise mechanisms governing CSFV budding remain inade quately understood. Our study elucidates that the endosomal sorting complex required for transport (ESCRT)-associated protein ALIX, in conjunction with ESCRT-III, plays a pivotal role in orchestrating CSFV budding. Genomic sequence analysis identified a critical interaction between the YPXnL late domain on the E2 protein and ALIX. Through immunoprecipitation and structural domain deletion assays, we demonstrated that the ALIX Bro1 domain specifically recognized viral particles by binding to the YPXnL motif. Immunoelectron and transmission electron microscopy further confirmed that, upon infection, ALIX accumulated at the periphery of subcellular organelles, including COPII vesicles, endosomes, and the Golgi apparatus, thereby facilitating CSFV budding. Our findings also revealed that ESCRT-III subunits CHMP2B, CHMP4B, CHMP7, and VPS4A interacted with ALIX to expedite CSFV budding. Notably, Rab8 activated by Kif4A contributed to the release of CSFV particles by interacting with ALIX and directing ALIX-containing vesicles along microtubules toward the cytosol. Our study demonstrates that ALIX specifically recognizes E2 and orchestrates the recruitment of ESCRT-III and Rab8 to facilitate the vesicular budding of CSFV particles from the Golgi apparatus to the cytosol. Ultimately, virus-laden vesicles propelled by Kif4A are transported along microtubules to the plasma membrane for release. Our findings offer the first compre hensive elucidation of the CSFV budding process and contribute to the identification of antiviral targets, thereby advancing the development of antiviral therapeutics.

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