Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation.
Calcium
/ metabolism
Calcium Signaling
/ physiology
Carrier Proteins
Hepacivirus
/ metabolism
Hepatitis C
Humans
Inflammasomes
/ metabolism
Interleukin-1beta
/ metabolism
Kupffer Cells
Liver
Liver Diseases
Macrophages
/ metabolism
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Primary Cell Culture
Reactive Oxygen Species
THP-1 Cells
/ metabolism
Type C Phospholipases
/ metabolism
Viral Core Proteins
/ metabolism
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
29
08
2018
accepted:
23
01
2019
entrez:
28
2
2019
pubmed:
28
2
2019
medline:
11
4
2019
Statut:
epublish
Résumé
Hepatitis C virus (HCV) infection remains a major cause of hepatic inflammation and liver disease. HCV triggers NLRP3 inflammasome activation and interleukin-1β (IL-1β) production from hepatic macrophages, or Kupffer cells, to drive the hepatic inflammatory response. Here we examined HCV activation of the NLRP3 inflammasome signaling cascade in primary human monocyte derived macrophages and THP-1 cell models of hepatic macrophages to define the HCV-specific agonist and cellular processes of inflammasome activation. We identified the HCV core protein as a virion-specific factor of inflammasome activation. The core protein was both necessary and sufficient for IL-1β production from macrophages exposed to HCV or soluble core protein alone. NLRP3 inflammasome activation by the HCV core protein required calcium mobilization linked with phospholipase-C activation. Our findings reveal a molecular basis of hepatic inflammasome activation and IL-1β release triggered by HCV core protein.
Identifiants
pubmed: 30811485
doi: 10.1371/journal.ppat.1007593
pii: PPATHOGENS-D-18-01704
pmc: PMC6392285
doi:
Substances chimiques
Carrier Proteins
0
Inflammasomes
0
Interleukin-1beta
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
NLRP3 protein, human
0
Reactive Oxygen Species
0
Viral Core Proteins
0
nucleocapsid protein, Hepatitis C virus
0
Type C Phospholipases
EC 3.1.4.-
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007593Subventions
Organisme : NIAID NIH HHS
ID : R01 AI118916
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127463
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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