State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.
Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
Virol Sin. 2021 Oct;36(5):1210-1219. doi: 10.1007/s12250-021-00377-9. Epub 2021 Jun 1.
Cholesterol-25-hydroxylase (CH25H) is a membrane protein associated with endoplasmic reticulum, and it is an interferon-stimulated factor regulated by interferon. CH25H catalyzes cholesterol to produce 25-hydroxycholesterol (25HC) by adding a second hydroxyl to the 25th carbon atom of cholesterol. Recent studies have shown that both CH25H and 25HC could inhibit the replication of many viruses. In this study, we found that ectopic expression of CH25H in HEK-293T and BHK-21 cell lines could inhibit the replication of Seneca Valley virus (SVV) and that there was no species difference. On the other hand, the knockdown of CH25H could enhance the replication of SVV in HEK-293T and BHK-21 cells, indicating the importance of CH25H. To some extent, the CH25H mutant without hydroxylase activity also lost its ability to inhibit SVV amplification. Further studies demonstrated that 25HC was involved in the entire life cycle of SVV, especially in repressing its adsorption process. This study reveals that CH25H exerts the advantage of innate immunity mainly by producing 25HC to block virion adsorption.
胆固醇-25-羟化酶（CH25H）是一种与内质网相关的膜蛋白，是一种干扰素调节的干扰素刺激因子。CH25H 通过在胆固醇的第 25 个碳原子上加第二个羟基，将胆固醇转化为 25-羟胆固醇（25HC）。最近的研究表明，CH25H 和 25HC 都可以抑制许多病毒的复制。在这项研究中，我们发现 CH25H 在 HEK-293T 和 BHK-21 细胞系中的异位表达可以抑制森那利瓦病毒（SVV）的复制，而且没有种属差异。另一方面，CH25H 的敲低可以增强 SVV 在 HEK-293T 和 BHK-21 细胞中的复制，表明 CH25H 的重要性。在某种程度上，没有羟化酶活性的 CH25H 突变体也失去了抑制 SVV 扩增的能力。进一步的研究表明，25HC 参与了 SVV 的整个生命周期，特别是在抑制其吸附过程中。这项研究表明，CH25H 主要通过产生 25HC 来阻断病毒吸附，从而发挥先天免疫优势。
