State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
Virus Res. 2021 Apr 2;295:198306. doi: 10.1016/j.virusres.2021.198306. Epub 2021 Jan 18.
Cholesterol 25-hydroxylase (CH25 H) is a key enzyme regulating cholesterol metabolism and also acts as a broad antiviral host restriction factor. Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that can cause vomiting, diarrhea, dehydration and even death in newborn piglets. In this study, we found that PDCoV infection significantly upregulated the expression of CH25H in IPI-FX cells, a cell line of porcine ileum epithelium. Overexpression of CH25H inhibited PDCoV replication, whereas CH25H silencing using RNA interference promoted PDCoV infection. Treatment with 25-hydroxycholesterol (25HC), the catalysate of cholesterol via CH25H, inhibited PDCoV proliferation by impairing viral invasion of IPI-FX cells. Furthermore, a mutant CH25H (CH25H-M) lacking hydroxylase activity also inhibited PDCoV infection to a lesser extent. Taken together, our data suggest that CH25H acts as a host restriction factor to inhibit the proliferation of PDCoV but this inhibitory effect is not completely dependent on its enzymatic activity.
胆固醇 25-羟化酶（CH25H）是调节胆固醇代谢的关键酶，也是一种广谱的抗病毒宿主限制因子。猪德尔塔冠状病毒（PDCoV）是一种新兴的猪肠道致病性冠状病毒，可导致新生仔猪呕吐、腹泻、脱水甚至死亡。在本研究中，我们发现 PDCoV 感染可显著上调猪回肠上皮细胞系 IPI-FX 中 CH25H 的表达。CH25H 的过表达抑制了 PDCoV 的复制，而 RNA 干扰沉默 CH25H 则促进了 PDCoV 的感染。25-羟胆固醇（25HC），即 CH25H 作用于胆固醇的产物，通过损害 PDCoV 对 IPI-FX 细胞的入侵，抑制了 PDCoV 的增殖。此外，缺乏羟化酶活性的突变 CH25H（CH25H-M）也在一定程度上抑制了 PDCoV 的感染。综上所述，我们的数据表明 CH25H 作为一种宿主限制因子抑制 PDCoV 的增殖，但这种抑制作用不完全依赖于其酶活性。
