G. Griffante  -  IFI16 Impacts Metabolic Reprogramming During Human Cytomegalovirus Infection
Channel: Icgeb
Date: 2023-01-30

Gloria Griffante, University of Piemonte Orientale, Novara, Italy speaks on "IFI16 Impacts Metabolic Reprogramming During Human Cytomegalovirus Infection".

Abstract: Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favours the envelopment of newly synthesized viral particles. As all cells are equipped with restriction factors (RFs) able to exert a protective effect against invading pathogens, we asked whether a similar defence mechanism would also be in place to preserve the metabolic compartment from HCMV infection. Here, we show that gamma interferon (IFN-γ)-inducible protein 16 (IFI16), an RF able to block HCMV DNA synthesis, can also counteract HCMV-mediated metabolic reprogramming in infected cells, thereby limiting virion infectivity. Specifically, we find that IFI16 downregulates the transcriptional activation of the glucose transporter 4 (GLUT4) through cooperation with the carbohydrate-response element-binding protein (ChREBP), thereby reducing HCMV-induced transcription of lipogenic enzymes. The resulting decrease in glucose uptake and consumption leads to diminished lipid synthesis, which ultimately curbs the de novo formation of enveloped viral particles in infected HFFs. Consistently, untargeted lipidomic analysis shows enhanced cholesteryl ester levels in IFI16 KO versus wild-type (WT) HFFs. Overall, our data unveil a new role of IFI16 in the regulation of glucose and lipid metabolism upon HCMV replication and uncover new potential targets for the development of novel antiviral therapies (mBio 2022).
Importance: HCMV is known to take advantage of the host cell also by inducing cellular metabolism to favour virion assembly. In this work the cellular restriction factor IFI16, induced by viral DNA and able to inhibit HCMV replication, is shown to be able to counteract such metabolic changes elicited by HCMV, thus revealing new promising targets for antiviral therapy.