Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou University, Yangzhou 225009, PR China.
Vet Microbiol. 2020 Jun;245:108658. doi: 10.1016/j.vetmic.2020.108658. Epub 2020 Apr 10.
Cholesterol-25-hydroxylase (CH25 H) is a reticulum-associated membrane protein induced by an important interferon-stimulating gene (ISG) and can significantly inhibit some virus replication. But the effect of CH25H on encephalomyocarditis virus (EMCV) is still not clear. In this study, we found that EMCV infection increases significantly the endogenous CH25H expression in BHK-21 and N2a cells. CH25H and cholesterol catalytic oxidation product 25-hydroxycholesterol (25HC) obviously inhibits EMCV infection by inhibiting the viral penetration. But the CH25H mutant lacking hydroxylase activity repairs the ability to inhibit the viral replication. Meanwhile, β-cyclodextrin crystalline as a cholesterol inhibitor significantly decreases the viral replication. In addition, CH25H can selectively interact and degrade the viral RNA-Dependent RNA Polymerase-3D protein by independent on the association of proteasome, lysosome and caspase manner. It provides new insights into the interplay mechanisms between CH25H and non-enveloped single-stranded positive RNA viruses.
胆固醇 25-羟化酶（CH25H）是一种内质网相关膜蛋白，由重要的干扰素刺激基因（ISG）诱导产生，可显著抑制某些病毒的复制。但 CH25H 对脑炎心肌炎病毒（EMCV）的影响尚不清楚。本研究发现，EMCV 感染显著增加 BHK-21 和 N2a 细胞内源性 CH25H 的表达。CH25H 和胆固醇催化氧化产物 25-羟胆固醇（25HC）通过抑制病毒渗透明显抑制 EMCV 感染。但缺乏羟化酶活性的 CH25H 突变体修复了抑制病毒复制的能力。同时，β-环糊精晶体作为胆固醇抑制剂，可显著降低病毒复制。此外，CH25H 可通过不依赖蛋白酶体、溶酶体和半胱天冬酶的方式选择性地与病毒 RNA 依赖性 RNA 聚合酶 3D 蛋白相互作用并降解。这为 CH25H 与无包膜单链正 RNA 病毒之间的相互作用机制提供了新的见解。
