Unique Substrate Preference of Serine-Palmitoyltransferease, Encoded by Marine Viruses, Modulates Host Sphingolipids to Determine the Fate of the Bloom-Forming Algae in the Oceans

The ubiquitous marine microalga Emiliania huxleyi forms massive seasonal blooms in the North Atlantic Ocean that impact nutrient recycling and earth climate. Recent observations have indicated the involvement of cocclithoviruses (EhV) in the coordinated rapid demise of these blooms. EhV are double stranded large DNA viruses composed of at least 2 internal lipid membranes, comprised largely of glycosphingolipids produced during infection. Interestingly, EhV’s genome encodes for almost the complete de novo sphingolipid biosynthetic pathway, never found in any known viral genome to date. Our previous work has demonstrated the involvement of a novel viral glycosphingolipid in inducing hallmarks of programmed cell death during the lytic viral infection of E. huxleyi host. Nevertheless, the molecular basis for sphingolipid biosynthesis and its biochemical coordination during host virus interactions are still underexplored.

De novo sphingolipid biosynthesis pathway is initiated by the rate limiting enzyme serine palmitoyltransferase (SPT). Our data indicate high expression of the viral SPT gene at early stages of infection. In vitro SPT activity assays suggest a shift in SPT substrate preference during infection, which is also reflected by the sphingoid-bases profile found in viral-infected algal cells. Furthermore, specific inhibition of SPT dramatically reduced extracellular viral release although did not affect intracellular viral DNA replication.

Our data suggests a unique mechanism of viral infection by which the infecting virus takes over the sphingolipid metabolism of the host, shifting its substrate specificity to produce viral-specific sphingolipids, which serve both as structural as well as signaling molecules to facilitate the viral reproduction.