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受丝氨酸蛋白酶 1(S1P)调控的胆固醇、脂肪酸和甘油三酯合成途径是严重发热伴血小板减少综合征病毒有效复制所必需的。

The cholesterol, fatty acid and triglyceride synthesis pathways regulated by site 1 protease (S1P) are required for efficient replication of severe fever with thrombocytopenia syndrome virus.

机构信息

Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Japan; National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Japan.

出版信息

Biochem Biophys Res Commun. 2018 Sep 5;503(2):631-636. doi: 10.1016/j.bbrc.2018.06.053. Epub 2018 Jun 14.

DOI:10.1016/j.bbrc.2018.06.053
PMID:29906459
Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively. These results enhance our understanding of the SFTSV replication mechanism and may contribute to the development of novel therapies for SFTSV infection.

摘要

严重发热伴血小板减少综合征(SFTS)是一种由 SFTS 病毒(SFTSV)引起的新发传染病,其死亡率很高。目前,尚无针对 SFTSV 感染的许可疫苗或治疗药物。在这里,我们报告说,由 S1P 调节的胆固醇、脂肪酸和甘油三酯合成途径参与 SFTSV 复制,使用 CHO-K1 细胞系(SRD-12B),该细胞系缺乏位点 1 蛋白酶(S1P)酶活性,PF-429242 是一种针对 S1P 酶活性的小分子化合物,以及 Fenofibrate 和 Lovastatin,分别抑制甘油三酯和胆固醇的合成。这些结果增强了我们对 SFTSV 复制机制的理解,并可能有助于开发针对 SFTSV 感染的新型治疗方法。

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