Multiple sphingolipid-metabolizing enzymes modulate influenza virus replication.

The sphingolipid network is sustained principally by the balance of bioactive sphingolipid molecules and their regulation by sphingolipid-metabolizing enzymes. The components in the lipid system display key functions in numerous cellular and disease conditions including virus infections. During the COVID-19 pandemic, there was a fruitful effort to use an inhibitor that blocks the activity of sphingosine kinase (SphK) 2 to cure the devastating disease. Support for the inhibitor came from pre-clinical research on influenza where the inhibitor demonstrated effective protection of mice from influenza-induced morbidity and mortality. This highlights the importance of basic and translational research on the sphingolipid system for improving human health. Multiple sphingolipid-metabolizing enzymes have been reported to regulate influenza virus replication and propagation. In this review, the emphasis is placed on the roles of these enzymes that impact influenza virus life cycle and the conceivable mechanisms for the interplay between influenza virus and the sphingolipid pathway.