PLoS. Pathog. 15, e1008199 (2019)

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As an enveloped virus, the dengue virus (DENV) relies on the lipid membrane of its host cells, either humans or Aedes Aegypti mosquitoes, and the virus reconfigures the lipidome in mosquito cells and midgut (where DENV first enters mosquitoes). To examine more closely how DENV alters lipids, Vial et al. used high-resolution mass spectrometry to monitor polar and non-polar Ae. Aegypti metabolites in midguts in whole mosquitoes and in an Ae. Aegypti cell line at post-infection time points representing the onset of replication through systemic infection. Of the various metabolite classes, the profiling showed that phospholipids (PL) were highly regulated throughout the DENV lifecycle, with aminophospholipids (aminoPL) and lysophospholipids specifically increased at the beginning of the life cycle and reduced at the end. Next, the authors found that the DENV-induced reconfiguration of the phospholipidome was associated with downregulation of AGPAT1, a rate-limiting enzyme for PL biosynthesis. AGPAT1 and AGPAT2 depletion in cells each caused unique increases in the levels of specific aminoPLs. In the case of AGPAT1 and its associated lipid changes, this caused an increase in DENV production. These findings suggest that DENV promotes increased aminoPL levels via AGPAT1 to support its own life cycle.