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

Xiaodong Zhuang; Andrea Magri; Michelle Hill; Alvina G. Lai; Abhinav Kumar; Srinivasa Bhargav Rambhatla; Claire L. Donald; Andrea F. Lopez-Clavijo; Simon Rudge; Katherine Pinnick; Wai Hoong Chang; Peter A.C. Wing; Ryan Brown; Ximing Qin; Peter Simmonds; Thomas F. Baumert; David Ray; Andrew Loudon; Peter Balfe; Michael Wakelam; Sam Butterworth; Alain Kohl; Catherine L. Jopling; Nicole Zitzmann; Jane A. McKeating

doi:10.1038/s41467-019-08299-7

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

Xiaodong Zhuang
, Andrea Magri
, Michelle Hill
, Alvina G. Lai
, Abhinav Kumar
, Srinivasa Bhargav Rambhatla
, Claire L. Donald
, Andrea F. Lopez-Clavijo
, Simon Rudge
, Katherine Pinnick
, Wai Hoong Chang
, Peter A.C. Wing
, Ryan Brown
, Ximing Qin
, Peter Simmonds
, Thomas F. Baumert
, David Ray
, Andrew Loudon
, Peter Balfe
, Michael Wakelam

Sam Butterworth, Alain Kohl, Catherine L. Jopling, Nicole Zitzmann, Jane A. McKeating

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

Abstract

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.

Original language	English
Article number	377
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08299-7
Publication status	Published - 1 Dec 2019
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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., ... McKeating, J. A. (2019). The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication. Nature Communications, 10(1), Article 377. https://doi.org/10.1038/s41467-019-08299-7

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title = "The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication",

abstract = "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.",

author = "Xiaodong Zhuang and Andrea Magri and Michelle Hill and Lai, \{Alvina G.\} and Abhinav Kumar and Rambhatla, \{Srinivasa Bhargav\} and Donald, \{Claire L.\} and Lopez-Clavijo, \{Andrea F.\} and Simon Rudge and Katherine Pinnick and Chang, \{Wai Hoong\} and Wing, \{Peter A.C.\} and Ryan Brown and Ximing Qin and Peter Simmonds and Baumert, \{Thomas F.\} and David Ray and Andrew Loudon and Peter Balfe and Michael Wakelam and Sam Butterworth and Alain Kohl and Jopling, \{Catherine L.\} and Nicole Zitzmann and McKeating, \{Jane A.\}",

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month = dec,

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doi = "10.1038/s41467-019-08299-7",

language = "English",

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Zhuang, X, Magri, A, Hill, M, Lai, AG, Kumar, A, Rambhatla, SB, Donald, CL, Lopez-Clavijo, AF, Rudge, S, Pinnick, K, Chang, WH, Wing, PAC, Brown, R, Qin, X, Simmonds, P, Baumert, TF, Ray, D, Loudon, A, Balfe, P, Wakelam, M, Butterworth, S, Kohl, A, Jopling, CL, Zitzmann, N & McKeating, JA 2019, 'The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication', Nature Communications, vol. 10, no. 1, 377. https://doi.org/10.1038/s41467-019-08299-7

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T1 - The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication

AU - Zhuang, Xiaodong

AU - Magri, Andrea

AU - Hill, Michelle

AU - Lai, Alvina G.

AU - Kumar, Abhinav

AU - Rambhatla, Srinivasa Bhargav

AU - Donald, Claire L.

AU - Lopez-Clavijo, Andrea F.

AU - Rudge, Simon

AU - Pinnick, Katherine

AU - Chang, Wai Hoong

AU - Wing, Peter A.C.

AU - Brown, Ryan

AU - Qin, Ximing

AU - Simmonds, Peter

AU - Baumert, Thomas F.

AU - Ray, David

AU - Loudon, Andrew

AU - Balfe, Peter

AU - Wakelam, Michael

AU - Butterworth, Sam

AU - Kohl, Alain

AU - Jopling, Catherine L.

AU - Zitzmann, Nicole

AU - McKeating, Jane A.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-08299-7

DO - 10.1038/s41467-019-08299-7

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 377

ER -

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

Abstract

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