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.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (31772749, 31572495), the Fundamental Research Funds for the Central Universities (2662017PY108), and Natural Science Foundation of Hubei Province (2019CFA010). Great gratitude goes to linguistics Professor Ping Liu from Foreign Language College, Huazhong Agriculture University, Wuhan, China for her work at English editing and language polishing.
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PQ, HC, and XL designed the research integrated the data, proofread and revised the manuscript. HL, ZZ, and LQ designed and performed the research, collected and analysed the data. HL drafted the manuscript. PQ finalized the manuscript. All authors read and approved the final version of the manuscript to be published.
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Li, H., Zhao, Z., Li, X. et al. Cholesterol-25-Hydroxylase Suppresses Seneca Valley Virus Infection via Producing 25-Hydroxycholesterol to Block Adsorption Procedure. Virol. Sin. 36, 1210–1219 (2021). https://doi.org/10.1007/s12250-021-00377-9
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DOI: https://doi.org/10.1007/s12250-021-00377-9