CIRI seminar: Dr. Jane McKEATING

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Date / Heure
Date(s) - 10/10/2019
11 h 00 min - 12 h 00 min

Amphi Pasteur, Tour CERVI

Dr. Jane McKEATING (Nuffield Department of Medicine, University of Oxford – UK) : “ Circadian regulation of virus replication ”

All living organisms follow a circadian rhythm that coordinates physiological, behavioural and biochemical responses to the environment. Such daily variations include the risk of infection and it is now well recognised that host innate and adaptive immune responses are circadian regulated and influence susceptibility to infectious agents and response to vaccines. Understanding the selective advantage the circadian clock confers on viral fitness will provide fundamental insights into virus-host cell interactions.
Circadian signalling pathways are primarily controlled by the transcription activators BMAL1 and CLOCK. The nuclear hormone receptors REV-ERBα and REV-ERBβ are BMAL1-responsive clock components that regulate metabolic gene expression in a circadian and tissue-dependent manner. We recently reported that REV-ERB regulates hepatocellular susceptibility to dengue virus, hepatitis C virus and zika virus replication, highlighting REV-ERB as a new restriction factor for flaviviruses.

         Short bio-sketch Jane Alison McKeating

Address: Nuffield Department of Medicine,
University of Oxford,
Old Road Campus, Headington,
Oxford, UK.

Email:                Tel No: +44(0)1865 612894

Scientific Summary
My research focuses on understanding early infection events that define the cellular and tissue tropism of clinically important human viruses to understand viral-associated pathology and to design anti-viral therapies. Our current focus is on hepatitis B and C viruses (HBV/HCV), the leading drivers for hepatocellular carcinoma, and includes studies on: (1) the role of inflammatory mediators in HIV/HCV or HBV co-infection and the impact of immune senescence; (2) the molecular pathways defining HBV and HCV transmission and impact of innate immune responses; (3) circadian clock control of HBV and HCV replication and (4) effect of low oxygen on HBV and HCV replication.

Selected publications:Selected papers from 182 peer reviewed publications with 16,696 citations and H index 68 (SCI)

Zhuang X, Magri A, Lai AG, Hill M, Chang WH, et al (2019) The circadian clock BMAL1 and REV-ERB regulate flavivirus replication. Nature Comms 10:377.

Wing PAC, Davenne T, Wettengel J, Lai AG, Chakraborty A, et al (2019). A dual role for SAMDH1 in HBV cccDNA synthesis and RT-dependent particle genesis. Life Science Alliance, in press.

Benedikz EK, Buckner MC, Blair JM, Wells TJ, Cook CNL, et al (2019). Bacterial flagellin enhances viral entry through toll-like receptor 5. Sci Reports. 9: 7903.

McNaughton AL, D’Arienzo V, Ansari A, Lumley S, Littlejohn M, et al. (2019). Unique, Tiny and misunderstood: insights into deep sequencing of the HBV genome. Gastroenterology 156: 84-399.

Zhuang X, Lai AG, McKeating JA, Rowe A and Balfe P. (2018) Daytime variation in hepatitis C virus replication kinetics post liver transplant. Wellcome Open Research, in press.

Ko C, Chakraborty A, Chou W-M, Hasreiter J, Wettengel JM, et al (2018). Hepatitis B virus capsid recycling and de novo secondary infection events maintain stable cccDNA levels. J Hepatology 69: 1231-1241.

Hedegaard DL, Tully DC, Rowe IA, Reynolds GM, Hu K, et al (2017). High resolution sequencing of hepatitis C virus reveals limited intra-hepatic compartmentalization during late stage liver disease. J Hepatology 66: 28-38.

Zhuang X, Rambhatla SB, Lai AG and McKeating JA. (2017) Interplay between circadian clock and viral infection. J Mol Med 95:1283

Farquhar M, Humphreys I, Rudge SA, Wilson G, Bhattacharya B, et al. (2017). Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication. J Hepatology 66: 919-929.

Vettori A, Greenald D, Wilson GK, Peron M. Facchinello, N, et al.  (2017) Glucocorticoids promote Von Hippel Lindau (pVHL) degradation and HIF1a stabilization. PNAS 114: 9948

Meredith LM, Hu K, Cheng X, Howard CR, Baumert TF, et al. (2016) Lentiviral hepatitis B pseudotypes uncover a role for NTCP and additional hepatocyte specific factors in virus entry. J Gen Virol 97: 121-7.

Rowe IA, Tulley D, Armstrong MJ, Parker R, Guo K, et al.  (2016) Effect of scavenger receptor BI antagonist ITX5061 on hepatitis C virus infection of the liver after transplantation. Liver Transplantation 22: 287.

Mailly L, Leboeuf C, Xiao F, Lupberger J, Wilson GK, et al. (2015). Clearance of persistent hepatitis C virus infection using a monoclonal antibody specific for tight junction protein Claudin-1. Nature Biotechnology 33: 549-54.

Fletcher NF, Sutaria R, Juandy J, Barnes A, Blahova M, Hu K, Cosset FL, Balfe P, Adams DH, Curbishley SM, Bertoletti A and McKeating JA. (2014). Activated macrophages promote hepatitis C virus entry in a tumor necrosis factor-dependent manner. Hepatology 59:1320-30.

Rowe IA, Wilson GK, Galsinh SK, Durrant S, Lazar C, et al.  (2014). Paracrine signals from liver sinusoidal endothelium regulate HCV replication. Hepatology 59: 375-84.

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