Lipidomics reveals the significance and mechanism of the cellular ceramide metabolism for rotavirus replication

文献类型： 外文期刊

第一作者： Tao, Ran

作者： Tao, Ran;Cheng, Xi;Gu, Laqiang;Zhou, Jinzhu;Zhu, Xuejiao;Zhang, Xuehan;Guo, Rongli;Wang, Wei;Li, Bin;Tao, Ran;Cheng, Xi;Gu, Laqiang;Zhou, Jinzhu;Zhu, Xuejiao;Zhang, Xuehan;Guo, Rongli;Wang, Wei;Li, Bin;Tao, Ran;Cheng, Xi;Gu, Laqiang;Zhou, Jinzhu;Zhu, Xuejiao;Zhang, Xuehan;Guo, Rongli;Wang, Wei;Li, Bin;Cheng, Xi;Li, Bin;Gu, Laqiang;Li, Bin

作者机构：

关键词： rotavirus; lipidomics; ceramide; inhibition; viral replication; apoptosis

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.4； 五年影响因子：4.9 ）

ISSN： 0022-538X

年卷期： 2024 年 98 卷 4 期

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收录情况： SCI

摘要： As one of the most important causative agents of severe gastroenteritis in children, piglets, and other young animals, species A rotaviruses have adversely impacted both human health and the global swine industry. Vaccines against rotaviruses (RVs) are insufficiently effective, and no specific treatment is available. To understand the relationships between porcine RV (PoRV) infection and enterocytes in terms of the cellular lipid metabolism, we performed an untargeted liquid chromatography mass spectrometry (LC-MS) lipidomics analysis of PoRV-infected IPEC-J2 cells. Herein, a total of 451 lipids (263 upregulated lipids and 188 downregulated lipids), spanning sphingolipid, glycerolipid, and glycerophospholipids, were significantly altered compared with the mock-infected group. Interestingly, almost all the ceramides among these lipids were upregulated during PoRV infection. LC-MS analysis was used to validated the lipidomics data and demonstrated that PoRV replication increased the levels of long-chain ceramides (C16-ceramide, C18-ceramide, and C24-ceramide) in cells. Furthermore, we found that these long-chain ceramides markedly inhibited PoRV infection and that their antiviral actions were exerted in the replication stage of PoRV infection. Moreover, downregulation of endogenous ceramides with the ceramide metabolic inhibitors enhanced PoRV propagation. Increasing the levels of ceramides by the addition of C6-ceramide strikingly suppressed the replication of diverse RV strains. We further found that the treatment with an apoptotic inhibitor could reverse the antiviral activity of ceramide against PoRV replication, demonstrating that ceramide restricted RV infection by inducing apoptosis. Altogether, this study revealed that ceramides played an antiviral role against RV infection, providing potential approaches for the development of antiviral therapies.

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