The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.
ARNTL Transcription Factors
/ genetics
Cell Line
Circadian Clocks
/ genetics
DNA Replication
Dengue
Dengue Virus
/ drug effects
Flavivirus
/ drug effects
Gene Expression Regulation
/ genetics
Genes, Essential
/ genetics
Hepacivirus
/ drug effects
Hepatitis C
Hepatocytes
/ immunology
Humans
Nuclear Receptor Subfamily 1, Group D, Member 1
/ genetics
Proteomics
RNA, Messenger
/ metabolism
Virus Internalization
/ drug effects
Virus Replication
/ drug effects
Zika Virus
/ drug effects
Zika Virus Infection
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 01 2019
22 01 2019
Historique:
received:
07
05
2018
accepted:
17
12
2018
entrez:
24
1
2019
pubmed:
24
1
2019
medline:
7
2
2019
Statut:
epublish
Résumé
The circadian clock regulates immune responses to microbes and affects pathogen replication, but the underlying molecular mechanisms are not well understood. Here we demonstrate that the circadian components BMAL1 and REV-ERBα influence several steps in the hepatitis C virus (HCV) life cycle, including particle entry into hepatocytes and RNA genome replication. Genetic knock out of Bmal1 and over-expression or activation of REV-ERB with synthetic agonists inhibits the replication of HCV and the related flaviruses dengue and Zika via perturbation of lipid signaling pathways. This study highlights a role for the circadian clock component REV-ERBα in regulating flavivirus replication.
Identifiants
pubmed: 30670689
doi: 10.1038/s41467-019-08299-7
pii: 10.1038/s41467-019-08299-7
pmc: PMC6343007
doi:
Substances chimiques
ARNTL Transcription Factors
0
BMAL1 protein, human
0
NR1D1 protein, human
0
Nuclear Receptor Subfamily 1, Group D, Member 1
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
377Subventions
Organisme : Medical Research Council
ID : MR/K01532X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15029
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100247
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P023576/1
Pays : United Kingdom
Organisme : European Research Council
ID : 671231
Pays : International
Organisme : Wellcome Trust
ID : 107851/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N017552/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008908/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M004821/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011853/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801976
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16056
Pays : United Kingdom
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