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Abstract
Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favors 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 defense mechanism would also be in place to preserve the metabolic compartment from HCMV infection. Here, we show that gamma interferon (IFN-g)-inducible protein 16 (IFI16), an RF able to block HCMV DNA synthesis, can also counteract HCMV-mediated metabolic reprogramming in infected primary human foreskin fibroblasts (HFFs), 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.
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Authors (17)
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Gloria Griffante
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Camilla Albano
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Francesca Gugliesi
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Selina Pasquero
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Sergio Fernando Castillo Pacheco
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Greta Bajetto
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Paolo Ettore Porporato
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Erica Mina
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Marta Vallino
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Christian Krapp
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Martin Roelsgaard Jakobsen
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John Purdy
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Jens Schneider von Deimling
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Santo Landolfo
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Valentina Dell’Oste
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Matteo Biolatti
Cite as
Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.1128/mbio.00435-22
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Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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mBio
no. 13,
ISSN: 2150-7511 - Language:
- English
- Publication year:
- 2022
- Bibliographic description:
- Griffante G., Hewelt-Belka W., Albano C., Gugliesi F., Pasquero S., Castillo Pacheco S. F., Bajetto G., Porporato P. E., Mina E., Vallino M., Krapp C., Jakobsen M. R., Purdy J., von Deimling J. S., Landolfo S., Dell’oste V., Biolatti M.: IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection// mBio -Vol. 13,iss. 3 (2022),
- DOI:
- Digital Object Identifier (open in new tab) 10.1128/mbio.00435-22
- Sources of funding:
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- Free publication
- Verified by:
- Gdańsk University of Technology
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