Integrated untargeted and targeted lipidomics discovers LPE 16:0 as a protector against respiratory syncytial virus infection.

ABSTRACT

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infections, imposing a substantial burden on healthcare systems globally. While lipid disorders have been observed in the lungs of infants and young children with RSV pneumonia, the specific characterization of these lipids and their roles in the development and progression of RSV pneumonia remain largely unexplored. To address this tissue, we established a non-targeted high-resolution lipidomics platform using UHPLC-Q-Exactive-MS to analyze lipid profiles in bronchoalveolar lavage fluid (BALF) obtained from mice infected with RSV. Through the lipidomics analysis, a total of 72 lipids species were identified, with 40 lipids were significantly changed. Notably, the primary changes were observed in ether phospholipids and lysophospholipids. Furthermore, a targeted lipidomics analysis utilizing UHPLC-QQQ-MS/MS was developed to specifically assess the levels of lysophospholipids, including lysophosphocholine 160 (LPC 160), lysophosphoethanolamine 160 (LPE 160) and lysophosphoglycerol 160 (LPG 160), in RSV-infected mice compared to control mice. Animal experiments revealed that LPE 160, rather than LPC 160 or LPG 160, provided protection against RSV-induced weight loss, reduced lung viral load, regulated immune cells and mitigated lung injury in mice afflicted with RSV pneumonia. In summary, our findings suggested that the host responses to RSV infection pathology are closely with various lipid metabolic. Additionally, our results elucidated novel biological functions of LPE 160 and offering new avenues for drug development against RSV pneumonia.