Division of Biologics Development, International Institute for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-ku, Sapporo, 001-0020, Japan.
Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Sci Rep. 2023 Aug 30;13(1):14210. doi: 10.1038/s41598-023-41055-y.
Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography-linear trap quadrupole-Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.
尽管已经证实流感病毒感染会影响脂质代谢，但具体细节仍不清楚。因此，我们通过非靶向脂质组学分析测量多种脂质分子种类，阐明了不同剂量甲型流感病毒 A/Puerto Rico/8/34（H1N1）（PR8）感染小鼠的动态脂质谱。将 C57BL/6 雄性小鼠用 PR8 病毒经鼻腔感染，分别以 50 或 500 噬菌斑形成单位（PFU）感染造成亚致死或致死性流感。在感染后 1、3 和 6 天（dpi）收集血浆和组织样本，并使用高效液相色谱-线性阱四极杆-Orbitrap 质谱联用以及基因表达分析进行综合脂质组学分析。在致死性感染小鼠的脂质谱中，最显著的特征是在 3 dpi 时含有多不饱和脂肪酸（PUFA）的磷脂酰乙醇胺（PE）的血浆浓度升高。此外，通过组织样本的基因表达和脂质组学分析表明，肺部而非肝脏中促进了含有 PUFA 的磷脂的产生。鉴于其他病毒感染患者，尤其是重症患者的血浆或血清中含有 PUFA 的 PE 水平升高，这些磷脂在循环中的升高可能是感染和传染病严重程度的生物标志物。
