Flavivirus modulation of cellular metabolism

• Flaviviruses modulate cellular metabolism to optimize their replication.
• DENV stimulates glycolysis.
• DENV induces lipid catabolism via selective autophagy.
• DENV NS3 enhances fatty acid synthesis at replication compartments.
• Replication compartments have altered lipid composition.

Over the last decade, we have begun to appreciate how flaviviruses manipulate cellular metabolism to establish an optimal environment for their replication. These metabolic changes include the stimulation of glycolysis, in addition to lipid anabolic and catabolic pathways. These processes are thought to promote an energetically favorable state, in addition to modifying membrane lipid composition for viral replication and virion envelopment. Importantly, many of these processes can be pharmacologically inhibited as successful antiviral strategies, at least in cell culture. In this review, we discuss the mechanisms by which flaviviruses alter cellular metabolism, remaining questions, and opportunities for therapeutic development.