All intracellular pathogens rely on metabolic pathways of the host for infection and replication. In the case of positive-strand RNA ((+)ssRNA) viruses, host cell lipids are directly needed formation of membranous replication organelles (ROs) and in the case of enveloped viruses for formation of the envelope. Additionally, viruses can induce mobilization and metabolization of lipids as building blocks and for energy that is needed for multiplication.
We performed shotgun lipidomics of cells infected with different flaviviruses including hepatitis C virus (HCV) that causes chronic infection and arthropod-borne orthoflaviviruses that cause acute infections. All viruses investigated induce profound lipid remodeling in infected cells. Altered lipid metabolic pathways were probed for mechanistic relevance using RNAi and specific inhibitors. These studies revealed that lipid remodeling by flavivirus infections includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.