HIF-1-mediated regulation of LDH gene unravels key insights into MCDV-1 pathogenesis in mud crabs Scylla paramamosain

文献类型： 外文期刊

第一作者： Jie, Yu-Kun

作者： Jie, Yu-Kun;Xie, Jia-Wei;Cheng, Chang-Hong;Jiang, Jian-Jun;Ma, Hong-Ling;Liu, Guang-Xin;Fan, Si-Gang;Deng, Yi-Qin;Feng, Juan;Guo, Zhi-Xun;Jie, Yu-Kun;Xie, Jia-Wei

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关键词： LDH; HIF-1; MCDV-1; Scylla paramamosain; Aerobic glycolysis

期刊名称：DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY （ 影响因子：2.9； 五年影响因子：3.1 ）

ISSN： 0145-305X

年卷期： 2024 年 153 卷

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收录情况： SCI

摘要： Hypoxia-inducible factors -1 (HIF-1) is a crucial transcription factor that regulates the expression of glycolytic genes. Our previous study proved that the Mud crab dicistrovirus-1 (MCDV-1) can induce aerobic glycolysis that favors viral replication in mud crab Scylla paramamosain. However, the role of HIF-1 on key glycolytic genes during the MCDV-1 infection has not been examined. In this study, the intricate interplay between HIF-1 and the key glycolysis enzyme, lactate dehydrogenase (LDH), was investigated after MCDV-1 infection. The expression of LDH was significant increased after MCDV-1 infection. Additionally, the expression of HIF-1 alpha was upregulated following MCDV-1 infection, potentially attributed to the downregulation of prolyl hydroxylase domains 2 expression. Subsequent examination of the SpLDH promoter identified the presence of hypoxia response elements (HREs), serving as binding sites for HIF-1 alpha. Intriguingly, experimental evidence demonstrated that SpHIF-1 alpha actively promotes SpLDH transcription through these HREs. To further elucidate the functional significance of SpHIF-1 alpha, targeted silencing was employed, resulting in a substantial reduction in SpLDH expression, activity, and lactate concentrations in MCDV-1-infected mud crabs. Notably, SpHIF-1 alpha-silenced mud crabs exhibited higher survival rates and lower viral loads in hepatopancreas tissues following MCDV-1 infection. These results highlight the critical role of SpHIF-1 alpha in MCDV-1 pathogenesis by regulating LDH gene dynamics, providing valuable insights into the molecular mechanisms underlying the virus-host interaction.

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