Cholesterol 25-Hydroxylase Suppresses Swine Acute Diarrhea Syndrome Coronavirus Infection by Blocking Spike Protein-Mediated Membrane Fusion

文献类型： 外文期刊

第一作者： Liu, Dakai

作者： Liu, Dakai;Shi, Da;Shi, Hongyan;Zhang, Liaoyuan;Zhang, Jiyu;Zeng, Miaomiao;Feng, Tingshuai;Yang, Xiaoman;Zhang, Xin;Chen, Jianfei;Jing, Zhaoyang;Ji, Zhaoyang;Zhang, Jialin;Feng, Li

作者机构：

关键词： cholesterol 25-hydroxylase; SADS-CoV; spike protein; membrane fusion

期刊名称：VIRUSES-BASEL （ 影响因子：4.7； 五年影响因子：4.8 ）

ISSN：

年卷期： 2023 年 15 卷 12 期

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收录情况： SCI

摘要： Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging porcine intestinal coronavirus that can cause acute diarrhea, vomiting, rapid weight loss, and high mortality in newborn piglets. Cholesterol 25-hydroxylase (CH25H) is a molecular mediator of innate antiviral immunity and converts cholesterol to 25-hydroxycholesterol (25HC). Previous studies have reported that CH25H and 25HC have an antiviral effect against multiple viruses. However, the interplay between SADS-CoV infection and CH25H or 25HC is still uncertain. Here, we found that CH25H and its enzymatic product 25HC restrained SADS-CoV replication by blocking membrane fusion. Our results show that CH25H was upregulated by SADS-CoV infection in vitro and in vivo, and that it was an IFN-stimulated gene in porcine ileum epithelial cells. Moreover, CH25H and CH25H mutants lacking catalytic activity can inhibit SADS-CoV replication. Furthermore, 25HC significantly suppressed SADS-CoV infection by inhibiting virus entry. Notably, we confirmed that CH25H and 25HC blocked SADS-CoV spike protein-mediated membrane fusion. Our data provide a possible antiviral therapy against SADS-CoV and other conceivable emerging coronaviruses in the future.

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