IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection - Publikacja - MOST Wiedzy

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IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection

Abstrakt

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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Accepted albo Published Version
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1128/mbio.00435-22
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Creative Commons: CC-BY otwiera się w nowej karcie

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
mBio nr 13,
ISSN: 2150-7511
Język:
angielski
Rok wydania:
2022
Opis bibliograficzny:
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:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1128/mbio.00435-22
Źródła finansowania:
  • Publikacja bezkosztowa
Weryfikacja:
Politechnika Gdańska

wyświetlono 97 razy

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