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

• Published in: Developmental and comparative immunology 2024-04, Vol.153, p.105127-105127, Article 105127
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Aerobic glycolysis; Animals; Brachyura - metabolism; crabs; Dicistroviridae; genes; glycolysis; hepatopancreas; HIF-1; host-pathogen relationships; Hypoxia; Hypoxia-Inducible Factor 1 - genetics; Hypoxia-Inducible Factor 1 - metabolism; immunology; L-Lactate Dehydrogenase - genetics; L-Lactate Dehydrogenase - metabolism; lactate dehydrogenase; lactic acid; Lactic Acid - metabolism; LDH; MCDV-1; Mud crab virus; pathogenesis; procollagen-proline dioxygenase; Scylla paramamosain; transcription factors; virus replication
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2023.105127

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-1α 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-1α. Intriguingly, experimental evidence demonstrated that SpHIF-1α actively promotes SpLDH transcription through these HREs. To further elucidate the functional significance of SpHIF-1α, targeted silencing was employed, resulting in a substantial reduction in SpLDH expression, activity, and lactate concentrations in MCDV-1-infected mud crabs. Notably, SpHIF-1α-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-1α in MCDV-1 pathogenesis by regulating LDH gene dynamics, providing valuable insights into the molecular mechanisms underlying the virus-host interaction. •The expression of SpHIF-1α and SpLDH is upregulated during MCDV-1 infection.•SpHIF-1α actively promotes SpLDH transcription through HREs.•SpHIF-1α plays a critical role in MCDV-1 pathogenesis by regulating LDH gene dynamics.