Fig. 6: Elevated ceramide levels increase ZIKV infection.

a KBM7 WT, SGMS1^GT, and SGMS1^GT + SGMS1 cells were infected with ZIKV (MOI = 1). At the indicated timepoints, culture supernatants were collected and titrated by plaque assay; n = 8 biological replicates. Two-way ANOVA with Dunnett’s multiple-comparison test. b KBM7 SGMS1^GT and SGMS1^GT + SGMS1 cells were infected with ZIKV (MOI = 1) and treated with 10 μM GW4869 or vehicle. At 24 hpi, supernatants were collected and analyzed by plaque assay; n = 6 independent infections. Two-tailed Student’s t test. c Huh7 cells were infected with ZIKV (MOI = 1) and treated with 10 μM GW4869 or recombinant neutral sphingomyelinase (SMase). At 24 hpi, culture supernatants were analyzed by plaque assay; n = 2 independent experiments. One-way ANOVA with Dunnett’s multiple-comparison test. d Model of experimental perturbations to the Cer/SM metabolic network and their effects on ZIKV replication. e Network of associations between disease modules similar to congenital ZIKV syndrome and lipid metabolism pathways. A metabolic network connecting the lipid subclasses identified by lipidomics was mapped to seven medical subject heading (MeSH) disease terms selected for their phenotypic similarity to clinical ZIKV syndrome. Nodes represent enzymes, lipids, and other metabolites in lipid biosynthesis, and gray lines represent reactions. Red nodes are metabolites associated with the MeSH ontologies linked by red lines. f Inset panel showing the metabolic neighborhood of the sphingolipids sphinganine and sphingosine. Data are mean ± SD. See also Supplementary Figs. 6–8, Supplementary Data 5, and the Source Data file.