Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Madrid, Spain.
Department of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, Spain.
Emerg Microbes Infect. 2023 Dec;12(2):2231556. doi: 10.1080/22221751.2023.2231556.
West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected mosquitoes. Severe forms of West Nile disease (WND) can curse with meningitis, encephalitis or acute flaccid paralysis. A better understanding of the physiopathology associated with disease progression is mandatory to find biomarkers and effective therapies. In this scenario, blood derivatives (plasma and serum) constitute the more commonly used biofluids due to its ease of collection and high value for diagnostic purposes. Therefore, the potential impact of this virus in the circulating lipidome was addressed combining the analysis of samples from experimentally infected mice and naturally WND patients. Our results unveil dynamic alterations in the lipidome that define specific metabolic fingerprints of different infection stages. Concomitant with neuroinvasion in mice, the lipid landscape was dominated by a metabolic reprograming that resulted in significant elevations of circulating sphingolipids (ceramides, dihydroceramides, and dihydrosphingomyelins), phosphatidylethanolamines and triacylglycerols. Remarkably, patients suffering from WND also displayed an elevation of ceramides, dihydroceramides, lactosylceramides, and monoacylglycerols in their sera. The dysregulation of sphingolipid metabolism by WNV may provide new therapeutic opportunities and supports the potential of certain lipids as novel peripheral biomarkers of WND progression.
西尼罗河病毒（WNV）是一种由受感染的蚊子叮咬传播的神经嗜性黄病毒。西尼罗河病（WND）的严重形式可能会导致脑膜炎、脑炎或急性弛缓性麻痹。更好地了解与疾病进展相关的病理生理学对于寻找生物标志物和有效疗法是必要的。在这种情况下，由于易于采集和具有较高的诊断价值，血液衍生物（血浆和血清）是更常用的生物流体。因此，通过结合对实验感染小鼠和自然发生的 WND 患者样本的分析，研究了该病毒对循环脂质组的潜在影响。我们的研究结果揭示了脂质组的动态变化，这些变化定义了不同感染阶段的特定代谢特征。与小鼠的神经入侵同时发生，脂质图谱被代谢重编程所主导，导致循环神经酰胺、二氢神经酰胺和二氢鞘氨醇、磷酸乙醇胺和三酰基甘油的显著升高。值得注意的是，患有 WND 的患者的血清中也显示出神经酰胺、二氢神经酰胺、乳糖基神经酰胺和单酰基甘油的升高。WNV 对神经酰胺代谢的失调可能为新的治疗机会提供了依据，并支持某些脂质作为 WND 进展的新型外周生物标志物的潜力。
