Šimečková et al.
Tick-borne encephalitis virus modulates sphingolipid and phospholipid metabolism in infected human neuronal cells.
Microb. Infect. 2024, in press, doi.org/10.1016/j.micinf.2024.105303.

TBE virus replication in the host cell is associated with extensive changes in cellular architecture., e.g. the endoplasmatic reticulum (ER) proliferates and is rearranged, and it is known that mosquito-borne flaviviral infection changes the lipid metabolis. So far, the lipid metabolism in TBE virus infected cell has not been studied in detail.

A study recently carried out showed that TBE virus induced changes in the phospholipid and sphingolipid metabolism in human neural cells. TBE virus infected cells showed an increased level in phosphotidylcholine, phosphatidylinositol and phosphatidylserine., indicating that the viral infection led to proliferation of cell membranes, including the ER membrane.

In addition, an increase of dihydroceramide levels was observed, which might be related to the membrane restructuring and autophagosome formation. While sphingosine, ceramide and glucosylceramide levels were increased, sphingosine-1-phosphate levels were slightly reduced.

Although the total amount of ceramides was increased, the authors did not find a fatty acid-length specificity. However, increased levels in C16 and C24 dihydroceramides and C16 ceramide might be involved in inducing autophagy.

To investigate the functional role of sphingolipids in TBE virus replication, infected cells were treated with an inhibitor of dihydroceramide desaturase, 4-HPR (fenretinide). Blocking the ceramide synthesis can affect the intracellular signaling mediated by sphingolipids, and this alters the fate of host-cell and/or TBE virus replication. Multiple mechanisms of action may be involved in the antiviral effect of 4-HPR inhibition of TBE virus. The results provide evidence for the importance of lipids in TBE virus replication. Targeting lipid metabolic pathways may be a promising pharmacological approach in anti-TBE virus research.

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