胆固醇 25-羟化酶通过酶活性依赖和非依赖机制抑制塞尼卡病毒 A 的复制。

Cholesterol 25-hydroxylase inhibits Senecavirus A replication by enzyme activity-dependent and independent mechanisms.

机构信息

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, China.

出版信息

Vet Microbiol. 2021 May;256:109038. doi: 10.1016/j.vetmic.2021.109038. Epub 2021 Mar 17.

DOI:10.1016/j.vetmic.2021.109038

PMID:33845332

Abstract

Cholesterol 25-hydroxylase (CH25 H), as a host restriction factor, has been reported to take a broad-spectrum antiviral effect. However, the role of CH25H in Senecavirus A (SVA) infection remains unknown. In this study, we first demonstrate that overexpression of CH25H inhibits SVA replication. Consistently, knockdown or knockout of the endogens CH25H promotes SVA infection. Further, the anti-SVA effect of 25-hydroxycholesterol (25HC), which is the product of CH25H, operates via inhibition of viral attachment and replication. On the other hand, the CH25H mutant (CH25H-M) lacking hydroxylase activity still restricts SVA infection, which can selectively interact and degrade SVA 3A protein via the ubiquitin-proteasome manner. Altogether, these results suggest that CH25H has an antiviral function in SVA infection and provides an alternative manner to control SVA.

摘要

胆固醇 25-羟化酶（CH25H）作为一种宿主限制因子，已被报道具有广谱抗病毒作用。然而，CH25H 在单纯疱疹病毒 A（SVA）感染中的作用尚不清楚。在本研究中，我们首先证明了 CH25H 的过表达抑制了 SVA 的复制。一致地，内源性 CH25H 的敲低或敲除促进了 SVA 感染。此外，CH25H 的产物 25-羟基胆固醇（25HC）通过抑制病毒附着和复制发挥抗 SVA 作用。另一方面，缺乏羟化酶活性的 CH25H 突变体（CH25H-M）仍然限制了 SVA 的感染，它可以通过泛素-蛋白酶体途径选择性地相互作用并降解 SVA 3A 蛋白。总之，这些结果表明 CH25H 在 SVA 感染中具有抗病毒功能，并提供了一种控制 SVA 的替代方式。