The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication

Autor: Zhuang, Xiaodong, Magri, Andrea, Hill, Michelle, Lai, Alvina G., Kumar, Abhinav, Rambhatla, Srinivasa Bhargav, Donald, Claire L., Lopez-Clavijo, Andrea F., Rudge, Simon, Pinnick, Katherine, Chang, Wai Hoong, Wing, Peter A. C., Brown, Ryan, Qin, Ximing, Simmonds, Peter, Baumert, Thomas F., Ray, David, Loudon, Andrew, Balfe, Peter, Wakelam, Michael, Butterworth, Sam, Kohl, Alain, Jopling, Catherine L., Zitzmann, Nicole, McKeating, Jane A.
Přispěvatelé: Donald, Claire L [0000-0002-4370-0707], Qin, Ximing [0000-0003-2496-2434], Ray, David [0000-0002-4739-6773], Balfe, Peter [0000-0002-6246-0876], Zitzmann, Nicole [0000-0003-1969-4949], Apollo - University of Cambridge Repository, University of Oxford, University of Birmingham [Birmingham], University of Glasgow, The Babraham Institute [Cambridge, UK], Anhui University [Hefei], Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Manchester [Manchester], University of Nottingham, UK (UON), univOAK, Archive ouverte
Rok vydání: 2019
Předmět:
Proteomics
Lydia Becker Institute
viruses
Aucun
Messenger/metabolism
Hepacivirus
Virus Replication
Dengue
Group D
Circadian Clocks/*genetics/immunology
Essential/genetics
lcsh:Science
ARNTL Transcription Factors/*genetics/immunology/pharmacology
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Genes
Essential
Zika Virus Infection
ARNTL Transcription Factors
virus diseases
Hepatitis C
Manchester Institute for Collaborative Research on Ageing
Dengue Virus/drug effects/genetics
Flavivirus/drug effects/*genetics/metabolism/pathogenicity
DNA Replication
ResearchInstitutes_Networks_Beacons/MICRA
Nuclear Receptor Subfamily 1
Science
Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Gene Expression Regulation/genetics
Article
Hepatocytes/immunology/virology
Cell Line
ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation
Circadian Clocks
Humans
RNA
Messenger
Zika Virus/drug effects/genetics
Flavivirus
Zika Virus
Dengue Virus
Virus Internalization
Member 1/*genetics/immunology/pharmacology
Virus Replication/*drug effects
Virus Internalization/drug effects
Genes
Gene Expression Regulation
Hepacivirus/drug effects/genetics/metabolism
Nuclear Receptor Subfamily 1
Group D
Member 1
Hepatocytes
RNA
lcsh:Q
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019)
Nature Communications
Nature Communications, 2019, 10 (1), ⟨10.1038/s41467-019-08299-7⟩
Nature Communications, Nature Publishing Group, 2019, 10 (1), ⟨10.1038/s41467-019-08299-7⟩
Zhuang, X, Magri, A, Hill, M, Lai, A G, Kumar, A, Rambhatla, S B, Donald, C L, Lopez-Clavijo, A F, Rudge, S, Pinnick, K, Chang, W H, Wing, P A C, Brown, R, Qin, X, Simmonds, P, Baumert, T F, Ray, D, Loudon, A, Balfe, P, Wakelam, M, Butterworth, S, Kohl, A, Jopling, C L, Zitzmann, N & McKeating, J A 2019, ' The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication ', Nature Communications, vol. 10, no. 1, pp. 377 . https://doi.org/10.1038/s41467-019-08299-7
ISSN: 2041-1723
DOI: 10.1038/s41467-019-08299-7⟩
Popis: 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.
The circadian clock can affect pathogen replication, but underlying molecular mechanisms are unclear. Here the authors demonstrate that the circadian components BMAL1 and REV-ERBα affect entry of hepatitis C virus (HCV) into hepatocytes and genome replication of HCV and related flaviviruses dengue and zika.
Databáze: OpenAIRE
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