State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.
Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.
Arch Virol. 2019 Dec;164(12):2963-2974. doi: 10.1007/s00705-019-04415-6. Epub 2019 Sep 24.
Cholesterol-25-hydroxylase (CH25H) is a reticulum-associated membrane protein that catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25HC). Recent studies have revealed that CH25H is an interferon-stimulated gene (ISG) that suppresses infection by several viruses. In the present study, we found that overexpression of both human and murine CH25H inhibited rabies virus (RABV) infection in HEK-293T (293T) cells. In contrast, silencing of CH25H enhanced RABV replication in 293T cells, and a catalytic mutant of CH25H lost its ability to inhibit RABV infection. Treatment with the oxysterol 25-hydroxycholesterol (25HC), the product of CH25H, dramatically decreased RABV replication in 293T, BSR and N2a cells by inhibiting viral membrane penetration. These data provide insights into the antiviral function of CH25H against RABV infection, which can potentially be used as a therapeutic agent for rabies.
胆固醇-25-羟化酶（CH25H）是一种内质网相关的膜蛋白，可催化胆固醇氧化为 25-羟胆固醇（25HC）。最近的研究表明，CH25H 是一种干扰素刺激基因（ISG），可抑制多种病毒的感染。在本研究中，我们发现人源和鼠源 CH25H 的过表达均可抑制 HEK-293T（293T）细胞中的狂犬病病毒（RABV）感染。相反，CH25H 的沉默增强了 293T 细胞中的 RABV 复制，而 CH25H 的催化突变体丧失了抑制 RABV 感染的能力。用 CH25H 的产物氧化固醇 25-羟胆固醇（25HC）处理可显著抑制 293T、BSR 和 N2a 细胞中的 RABV 复制，通过抑制病毒膜穿透发挥抗病毒作用。这些数据为 CH25H 抑制 RABV 感染的抗病毒功能提供了新的见解，有望成为狂犬病的治疗药物。
