Virus-induced glycolysis-mediated histone lactylation promotes virus infection in shrimp via the S6K2 pathway [RNAseq]. Penaeus japonicus

As non-cellular organisms, viruses need to infect living cells to survive themselves. The virus infection must alter the host metabolisms. However, the influence of the metabolites from the altered metabolisms of virus-infected host cells on virus-host interactions remains largely unclear. To address this issue, a crustacean shrimp was challenged with white spot syndrome virus (WSSV) in this study. The in vivo results presented that the WSSV infection enhanced shrimp glycolysis, leading to the accumulation of lactate. The lactate accumulation in turn promoted the site-specific histone lactylation (H3K18la and H4K12la). To explore which target genes are affected by H3K18la or H4K12la, at 48 hours after WSSV infection, the shrimp hemocytes were collected and performed genome-wide CUT&Tag and RNA-seq analysis to identify candidate genes regulated by H4K12la or H3K18la. Therefore, our findings contributed novel insights into the effects and the underlying mechanism of the virus-induced metabolites on the virus-host interactions, providing new targets for the control of virus infection.

作为非细胞型生物，病毒必须侵染活细胞才能维持自身存活。病毒侵染宿主后必然会改变宿主的代谢过程，然而，病毒侵染宿主后宿主代谢发生改变所产生的代谢物，其对病毒-宿主互作的影响在很大程度上仍未得到阐明。为解决这一科学问题，本研究以甲壳类动物虾为实验对象，采用白斑综合征病毒（White Spot Syndrome Virus, WSSV）进行攻毒处理。体内实验结果显示，WSSV侵染可增强虾的糖酵解通路活性，进而导致乳酸积累。乳酸积累又会进一步促进位点特异性的组蛋白乳酸化（histone lactylation）修饰（H3K18la与H4K12la）。为探究受H3K18la或H4K12la调控的靶基因，本研究在WSSV侵染后48小时采集虾的血淋巴细胞，并开展全基因组范围的CUT&Tag与RNA测序（RNA-seq）分析，筛选得到受H3K18la或H4K12la调控的候选基因。综上，本研究的发现为病毒诱导产生的代谢物对病毒-宿主互作的影响及其潜在分子机制提供了全新的见解，同时为病毒侵染的防控提供了新的潜在靶点。