Phospholipidomic identification of potential serum biomarkers in dengue fever, hepatitis B and hepatitis C using liquid chromatography-electrospray ionization-tandem mass spectrometry

Metabolomic Insights into Human Arboviral Infections: Dengue, Chikungunya, and Zika Viruses

“…Intracellular levels of the most abundant membrane glycerophospholipid, PC, increased during infection with DENVs, WNV and ZIKV [19,82,121,124]. Flavivirus infection of humans, humanized mice, and cell culture often altered levels of glycerophospholipids that curve membranes or control membrane fluidity, such as PI, PE, LPL, and sphingolipids, consistent with the need for flexible, curved membranes for replication spherules and virion envelopes [11,20,22,27,28,85,87,93,121,123,134]. Sphingolipid and LPL production are also important for viral multiplication, as inhibiting their metabolic conversions decreased flavivirus multiplication [97,121,123].…”

“…The timing of these changes connected elevated SM with the early host response while increased LPE levels correlated to later responses, and thus these lipids may have potential as prognostic biomarkers [20]. Khedr et al [85] also found four of the same LPCs similarly decreased during infection with DENVs in adult sera relative to healthy controls. LPCs have also been shown to have prognostic potential in a cohort of children in Nicaragua with DENV2 [22].…”

“…Glycerophospholipids can also differentiate viral diseases. Khedr et al [85] used LC-MS/MS to quantify glycerophospholipids in sera from healthy controls and patients diagnosed with DF, hepatitis B, or hepatitis C. The authors attributed the decreased PIs and PE in DF patients compared to healthy controls to phospholipase A2 activation by DENVs, which would convert them to lysophosphatidylinositols (LPI) and LPE [85,91]. Indeed, virus infection increased the amount of LPI(16:0), a potential product of phospholipase A2 activity on the PIs.…”

“…Indeed, virus infection increased the amount of LPI(16:0), a potential product of phospholipase A2 activity on the PIs. PSs and LPCs were also less abundant during DF than in healthy controls [85]. Levels of several PCs, PE(38:4), and PS(36:2) were higher and levels of LPCs were lower in DF patients than those of hepatitis B or hepatitis C patients, thereby differentiating these viral diseases [85].…”

“…In rats, Chang et al (2017) demonstrated that liver fibrosis altered the TCA cycle as well as tryptophan, glycerophospholipid, and sphingolipid metabolism [106]. These same pathways were also altered in humans and mice infected by DENVs, suggesting that DENVs induce liver damage [20,21,22,23,25,27,85,90,93,95,96]. Levels of bile acids, acylcarnitines, and acetate were also increased in the sera of humans infected with DENVs, similarly suggesting liver damage [20,21,25].…”