Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx.
Animals
Mice
Glycerol
/ metabolism
Glycerolphosphate Dehydrogenase
/ metabolism
Hepatitis B
/ metabolism
Hepatitis B virus
/ physiology
Mitochondria
/ enzymology
Phosphates
/ metabolism
Tripartite Motif-Containing Protein 28
/ metabolism
Viral Regulatory and Accessory Proteins
/ genetics
Virus Replication
GPD2
HBx
TRIM28
mitochondria
ubiquitin-dependent degradation
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
31 05 2023
31 05 2023
Historique:
medline:
2
6
2023
pubmed:
11
5
2023
entrez:
11
5
2023
Statut:
ppublish
Résumé
Hepatitis B virus (HBV) infection affects hepatic metabolism. Serum metabolomics studies have suggested that HBV possibly hijacks the glycerol-3-phosphate (G3P) shuttle. In this study, the two glycerol-3-phosphate dehydrogenases (GPD1 and GPD2) in the G3P shuttle were analyzed for determining their role in HBV replication and the findings revealed that GPD2 and not GPD1 inhibited HBV replication. The knockdown of GPD2 expression upregulated HBV replication, while GPD2 overexpression reduced HBV replication. Moreover, the overexpression of GPD2 significantly reduced HBV replication in hydrodynamic injection-based mouse models. Mechanistically, this inhibitory effect is related to the GPD2-mediated degradation of HBx protein by recruiting the E3 ubiquitin ligase TRIM28 and not to the alterations in G3P metabolism. In conclusion, this study revealed GPD2, a key enzyme in the G3P shuttle, as a host restriction factor in HBV replication.
Identifiants
pubmed: 37166302
doi: 10.1128/jvi.00580-23
pmc: PMC10231258
doi:
Substances chimiques
Glycerol
PDC6A3C0OX
Glycerolphosphate Dehydrogenase
EC 1.1.-
Phosphates
0
Trim28 protein, mouse
EC 2.3.2.27
Tripartite Motif-Containing Protein 28
EC 2.3.2.27
Viral Regulatory and Accessory Proteins
0
hepatitis B virus X protein
0
Gpd2 protein, mouse
EC 1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0058023Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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