Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection. Increased lipogenesis occurs upon HCMV infection most likely to favor the envelopment of newly synthesized particles. Here, we demonstrate that IFN-γ-inducible protein 16 (IFI16), previously characterized as a restriction factor of HCMV replication, interferes with metabolic pathways during infection. Specifically, we report that IFI16 hampers glucose uptake after HCMV infection by inhibiting the expression of the glucose transporter (GLUT) 4, resulting in decreased glucose consumption. GLUT4 downregulation is induced by a cooperation between IFI16 and the carbohydrate-response element-binding protein (ChREBP) on the GLUT4 promoter. Consequently, IFI16 reduces the transcription of the genes encoding lipogenic enzymes, leading to a decreased lipid synthesis and a reduced amount of enveloped viral particles in the infected cells. Finally, an untargeted lipidomic approach highlights the differences in lipid composition between WT and IFI16 KO cells particularly significantly increased cholesteryl esters content in IFI16 KO cells in comparison to WT cells. Overall, our data unravel a new role for IFI16 in the regulation of glucose and lipid metabolism upon HCMV replication and shed light for new promising targets in antiviral therapy.

IFI16 is a Negative Regulator of Glucose and Cellular Lipid Metabolism during Human Cytomegalovirus Infection

Matteo Biolatti;Gloria Griffante;Camilla Albano;Francesca Gugliesi;Selina Pasquero;Sergio Castillo Pacheco;Paolo Porporato;Erica Mina;Santo Landolfo;Valentina Dell’Oste
2021

Abstract

Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection. Increased lipogenesis occurs upon HCMV infection most likely to favor the envelopment of newly synthesized particles. Here, we demonstrate that IFN-γ-inducible protein 16 (IFI16), previously characterized as a restriction factor of HCMV replication, interferes with metabolic pathways during infection. Specifically, we report that IFI16 hampers glucose uptake after HCMV infection by inhibiting the expression of the glucose transporter (GLUT) 4, resulting in decreased glucose consumption. GLUT4 downregulation is induced by a cooperation between IFI16 and the carbohydrate-response element-binding protein (ChREBP) on the GLUT4 promoter. Consequently, IFI16 reduces the transcription of the genes encoding lipogenic enzymes, leading to a decreased lipid synthesis and a reduced amount of enveloped viral particles in the infected cells. Finally, an untargeted lipidomic approach highlights the differences in lipid composition between WT and IFI16 KO cells particularly significantly increased cholesteryl esters content in IFI16 KO cells in comparison to WT cells. Overall, our data unravel a new role for IFI16 in the regulation of glucose and lipid metabolism upon HCMV replication and shed light for new promising targets in antiviral therapy.
45th International Herpesvirus Workshop
Virtuale
02/08/2021 - 06/08/2021
45th International Herpesvirus Workshop - Abstract Book
211
211
Matteo Biolatti, Gloria Griffante, Camilla Albano, Francesca Gugliesi, Selina Pasquero, Sergio Castillo Pacheco, Paolo Porporato, Erica Mina, Weronika Hewelt-Belka, Marta Vallino, Christian Krapp, Martin Jakobsen, John Purdy, Santo Landolfo, Valentina Dell’Oste
File in questo prodotto:
File Dimensione Formato  
IHW 2021 Abstract Book Final.pdf

Accesso aperto

Dimensione 579.96 kB
Formato Adobe PDF
579.96 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1799682
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact