Metabolic Games: IFI16-Driven Regulation of Cellular Metabolism upon HCMV Infection

Cellular lipid metabolism plays a pivotal role upon human cytomegalovirus (HCMV) infection. Indeed, HCMV infection has been associated with the increased lipogenesis in infected cells that is likely required for the envelopment of the newly formed virions. Here, we demonstrate that IFN-γ-inducible protein 16 (IFI16), previously reported as a restriction factor of HCMV replication, modulates various cell functions and interferes with metabolic pathways during HCMV infection. Specifically, we report that IFI16 reduces the expression of the glucose transporter GLUT4, resulting in decreased glucose import and translocation of the carbohydrate-response element binding protein (ChREBP) to the nucleus. Consequently, reduced transcription of the genes encoding lipogenic enzymes leads to decreased lipid synthesis and enhanced generation of the enveloped viral particles in infected cells. These data may shed light on the potential impact of IFI16 on regulation of glucose and lipid metabolism upon HCMV replication suggesting new promising targets for antiviral therapy.