State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan, China.
Int J Biol Sci. 2022 Jul 11;18(12):4744-4755. doi: 10.7150/ijbs.73057. eCollection 2022.
Viruses exploit the host lipid metabolism machinery to achieve efficient replication. We herein characterize the lipids profile reprogramming and using liquid chromatography-mass spectrometry-based untargeted lipidomics. The lipidome of SARS-CoV-2-infected Caco-2 cells was markedly different from that of mock-infected samples, with most of the changes involving downregulation of ceramides. In COVID-19 patients' plasma samples, a total of 54 lipids belonging to 12 lipid classes that were significantly perturbed compared to non-infected control subjects' plasma samples were identified. Among these 12 lipid classes, ether-linked phosphatidylcholines, ether-linked phosphatidylethanolamines, phosphatidylcholines, and ceramides were the four most perturbed. Pathway analysis revealed that the glycerophospholipid, sphingolipid, and ether lipid metabolisms pathway were the most significantly perturbed host pathways. Phosphatidic acid phosphatases (PAP) were involved in all three pathways and PAP-1 deficiency significantly suppressed SARS-CoV-2 replication. siRNA knockdown of LPIN2 and LPIN3 resulted in significant reduction of SARS-CoV-2 load. In summary, these findings characterized the host lipidomic changes upon SARS-CoV-2 infection and identified PAP-1 as a potential target for intervention for COVID-19.
病毒利用宿主脂质代谢机制实现高效复制。本研究采用基于液相色谱-质谱的非靶向脂质组学方法，对 SARS-CoV-2 感染 Caco-2 细胞后的脂质谱重编程进行了表征。与 mock 感染的样本相比，SARS-CoV-2 感染的 Caco-2 细胞的脂质组明显不同，大多数变化涉及神经酰胺的下调。在 COVID-19 患者的血浆样本中，与未感染对照的血浆样本相比，共鉴定出 54 种脂质，它们属于 12 种脂质类别，存在显著差异。在这 12 种脂质类别中，醚连接的磷脂酰胆碱、醚连接的磷脂酰乙醇胺、磷脂酰胆碱和神经酰胺是受干扰最严重的四种。通路分析显示，甘油磷脂、鞘脂和醚脂代谢途径是受干扰最严重的宿主途径。磷酸酶酰基转移酶 (PAP) 参与了这三个途径，PAP-1 缺乏显著抑制了 SARS-CoV-2 的复制。siRNA 敲低 LPIN2 和 LPIN3 导致 SARS-CoV-2 载量显著减少。综上所述，这些发现描述了 SARS-CoV-2 感染后宿主脂质组的变化，并确定 PAP-1 是 COVID-19 干预的潜在靶点。
