1. Academic Validation
  2. Cholesterol-25-Hydroxylase Suppresses Seneca Valley Virus Infection via Producing 25-Hydroxycholesterol to Block Adsorption Procedure

Cholesterol-25-Hydroxylase Suppresses Seneca Valley Virus Infection via Producing 25-Hydroxycholesterol to Block Adsorption Procedure

  • Virol Sin. 2021 Oct;36(5):1210-1219. doi: 10.1007/s12250-021-00377-9.
Hui Li  # 1 2 Zekai Zhao  # 1 2 Xiangmin Li 1 2 3 Liuxing Qin 1 2 Wei Wen 1 2 Huanchun Chen 1 2 3 Ping Qian 4 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.
  • 2 Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  • 3 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
  • 4 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China. qianp@mail.hzau.edu.cn.
  • 5 Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. qianp@mail.hzau.edu.cn.
  • 6 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. qianp@mail.hzau.edu.cn.
  • # Contributed equally.
Abstract

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.

Keywords

25-hydroxycholesterol (25HC); Cholesterol-25-hydroxylase (CH25H); Seneca Valley virus (SVV).

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