Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition.
Adaptor Proteins, Signal Transducing
/ metabolism
Anaerobiosis
Animals
Cells, Cultured
DEAD Box Protein 58
/ metabolism
Glucose
/ metabolism
Glycolysis
Hep G2 Cells
Hepatitis B virus
/ physiology
Hepatocytes
/ metabolism
Humans
Immune Evasion
Immunity, Innate
Interferons
/ metabolism
Lactic Acid
/ metabolism
Metabolome
Mice, Inbred C57BL
Models, Biological
Signal Transduction
Virion
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 01 2021
04 01 2021
Historique:
received:
14
12
2019
accepted:
23
11
2020
entrez:
5
1
2021
pubmed:
6
1
2021
medline:
15
1
2021
Statut:
epublish
Résumé
Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and how the two systems interact with each other during hepatitis B virus (HBV) infections and, if so, which mechanisms are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using a series of pharmacological and genetic approaches, we provide in vitro and in vivo evidence indicating that HBV suppresses RLR signaling via lactate dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS preventing its aggregation and mitochondrial localization during HBV infection. Therefore, we show that HK2 and glycolysis-derived lactate have important functions in the immune escape of HBV and that energy metabolism regulates innate immunity during HBV infection.
Identifiants
pubmed: 33397935
doi: 10.1038/s41467-020-20316-8
pii: 10.1038/s41467-020-20316-8
pmc: PMC7782485
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
MAVS protein, human
0
Lactic Acid
33X04XA5AT
Interferons
9008-11-1
DEAD Box Protein 58
EC 3.6.4.13
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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