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3) Elucidating the lipid metabolic remodeling during positive-sense RNA virus replication and analyzing the role of lipid metabolic processes in virus replication

Foto: Sascha Mannel

Pathogens hijack lipid metabolic pathways for replication and/or persistent infection. We hypothesize that positive-sense RNA viruses require similar lipid metabolic pathways for replication. We recently investigated in-depth the HCV-induced changes in the lipid composition and performed quantitative shotgun lipidomic studies of whole cell extracts and subcellular compartments (Hofmann et al., Biochim. Biophys. Acta, 2018). Our results indicate that HCV infection reduces the ratio of neutral to membrane lipids. While the amount of neutral lipids was unchanged, membrane lipids, especially cholesterol and phospholipids, accumulated in the microsomal fraction in HCV-infected cells. In addition, HCV-infected cells had a higher abundance of phospholipids and triglycerides with longer fatty acyl chains and depletion of fatty acid elongases impaired HCV replication. Likewise, we detected an accumulation of oleic acid-containing lipid species and found that inhibition of the responsible desaturase suppressed HCV replication. These results suggest that elongases and desaturases are host factors required for HCV efficient replication. We now determine similarities and differences in lipid metabolic remodeling induced by HCV and Flaviviruses such as DENV and ZIKV and between different host cell environments.