Dengue Virus-Induced Autophagy Regulates Lipid Metabolism

SummaryAutophagy influences numerous cellular processes, including innate and adaptive immunity against intracellular pathogens. However, some viruses, including dengue virus (DENV), usurp autophagy to enhance their replication. The mechanism for a positive role of autophagy in DENV infection is unclear. We present data that DENV induction of autophagy regulates cellular lipid metabolism. DENV infection leads to an autophagy-dependent processing of lipid droplets and triglycerides to release free fatty acids. This results in an increase in cellular β-oxidation, which generates ATP. These processes are required for efficient DENV replication. Importantly, exogenous fatty acids can supplant the requirement of autophagy in DENV replication. These results define a role for autophagy in DENV infection and provide a mechanism by which viruses can alter cellular lipid metabolism to promote their replication.

► DENV-induced autophagosomes partially colocalize with lipid droplets
► DENV-induced autophagy depletes lipid droplets and triglycerides
► Autophagy increases cellular β-oxidation, which is required for DENV replication
► Exogenous fatty acids supplant the requirement of autophagy for DENV replication