Chandran Kartik, Sullivan Nancy J, Felbor Ute, Whelan Sean P, Cunningham James M
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Science. 2005 Jun 10;308(5728):1643-5. doi: 10.1126/science.1110656. Epub 2005 Apr 14.
Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs.
埃博拉病毒（EboV）可导致人类迅速患上致命的出血热，目前尚无有效治疗方法。我们发现，携带埃博拉病毒糖蛋白（GP）的水疱性口炎病毒感染非洲绿猴肾（Vero）细胞需要内体半胱氨酸蛋白酶的活性。通过使用选择性蛋白酶抑制剂和蛋白酶缺陷细胞系，我们确定了组织蛋白酶B（CatB）在依赖埃博拉病毒GP的进入过程中的关键作用以及组织蛋白酶L（CatL）的辅助作用。生化研究表明，CatB和CatL通过对埃博拉病毒GP亚基GP1进行蛋白水解来介导进入，并支持一种多步骤机制，该机制解释了这些酶对感染的相对贡献。CatB和CatB/CatL抑制剂可减少感染性埃博拉病毒扎伊尔型在培养细胞中的增殖，可能值得作为抗埃博拉病毒药物进行研究。
