CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
PLoS Pathog. 2021 Mar 8;17(3):e1009393. doi: 10.1371/journal.ppat.1009393. eCollection 2021 Mar.
Classical swine fever virus (CSFV) is an important pathogen in the swine industry. Virion attachment is mediated by envelope proteins Erns and E2, and E2 is indispensable. Using a pull-down assay with soluble E2 as the bait, we demonstrated that ADAM17, a disintegrin and metalloproteinase 17, is essential for CSFV entry. Loss of ADAM17 in a permissive cell line eliminated E2 binding and viral entry, but compensation with pig ADAM17 cDNA completely rescued these phenotypes. Similarly, ADAM17 silencing in primary porcine fibroblasts significantly impaired virus infection. In addition, human and mouse ADAM17, which is highly homologous to pig ADAM17, also mediated CSFV entry. The metalloproteinase domain of ADAM17 bound directly to E2 protein in a zinc-dependent manner. A surface exposed region within this domain was mapped and shown to be critical for CSFV entry. These findings clearly demonstrate that ADAM17 serves as an essential attachment factor for CSFV.
经典猪瘟病毒（Classical swine fever virus，CSFV）是猪养殖业中的一种重要病原体。病毒粒子的附着是由包膜蛋白 Erns 和 E2 介导的，而 E2 是不可或缺的。我们使用可溶性 E2 作为诱饵的下拉测定法，证明了解整合素金属蛋白酶 17（ADAM17）对于 CSFV 的进入是必需的。在允许的细胞系中丧失 ADAM17 会消除 E2 结合和病毒进入，但用猪 ADAM17 cDNA 进行补偿则完全挽救了这些表型。同样，在原代猪成纤维细胞中沉默 ADAM17 会显著损害病毒感染。此外，与人 ADAM17 和鼠 ADAM17 高度同源的人类和鼠 ADAM17 也介导了 CSFV 的进入。ADAM17 的金属蛋白酶结构域以锌依赖性方式直接结合到 E2 蛋白上。该结构域内的一个暴露表面区域被映射并被证明对 CSFV 的进入至关重要。这些发现清楚地表明 ADAM17 是 CSFV 的一个重要附着因子。
