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

Author:

Liu Dakai1,Shi Da1,Shi Hongyan1,Zhang Liaoyuan1,Zhang Jiyu1,Zeng Miaomiao1,Feng Tingshuai1,Yang Xiaoman1,Zhang Xin1,Chen Jianfei1,Jing Zhaoyang1,Ji Zhaoyang1,Zhang Jialin1,Feng Li1ORCID

Affiliation:

1. State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xiangfang District, Haping Road 678, Harbin 150069, China

Abstract

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.

Funder

National Key R&D Program of China

Natural Science Foundation of Heilongjiang Province of China

Central Public-interest Scientific Institution Basal Research Found

Project of State Key Laboratory of Veterinary Biotechnology

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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