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HBV1 TERMINATED

Innate immune responses to human hepatotropic viral infections

Total Cost €

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EC-Contrib. €

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Partnership

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 HBV1 project word cloud

Explore the words cloud of the HBV1 project. It provides you a very rough idea of what is the project "HBV1" about.

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Project "HBV1" data sheet

The following table provides information about the project.

Coordinator
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙498˙312 €
 EC max contribution 1˙498˙312 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 1˙498˙312.00

Map

 Project objective

Chronic hepatotropic infections including hepatitis B (HBV) and C (HCV) are a major public health concern. Even though both viruses belong to completely distinct families the pathogenesis they elicit is strikingly similar, leading to liver fibrosis and cirrhosis. Treatment for HBV and HCV consists of either direct-acting antivirals or pegylated interferon (IFN)α. In contrast to HCV, these treatment regimen are noncurative for HBV. Little is known to date about the host/pathogen interactions determining viral persistence. Both viruses are sensitive to IFN, activating the JAK/STAT signalling pathway to activate interferonstimulated gene expression (ISG), which are ultimately acting as antiviral immune effectors. Nevertheless, neither type I or III IFN are very effective in their treatment. Here, we suggest investigating the mechanistic details of type I and type III IFN action on HCV and HBV in vitro and vivo with the goal of uncovering not only the differential ISG induction but furthermore characterise viral immune evasion strategies. Building on our previous success in dissecting the host response to HCV and creating the first immunocompetent mouse model for HCV we aim at using both, novel microfluidic culture systems based on 3D hepatocyte cultures susceptible to both HCV and HBV as well as human liver-chimeric mice in combination with single-cell analysis of the antiviral response against HBV and HCV elicited by type I and III IFN. Additionally, we will utilize lentiviral high throughput screening used previously for HCV to identify interferon effector molecules active against HBV. This project will not only provide new insights into the innate immune response to chronic hepatotropic virus infections but furthermore holds the potential of uncovering novel drug targets, aiding in the curative therapy for both, HCV and HBV and offer novel insights into vaccine design. This project has the aim of identifying novel host factors and drug targets enabling the development of immunomodulatory antiviral drugs. This ranks the scope of the proposal between LS6 Immunity and Infection and LS9 Applied Life Sciences and Non-Medical Biotechnology. Evaluating novel bioengineered human liver culture systems and building on human liver-chimeric mice clearly places this proposal at the forefront of identifying novel drug targets and assisting in the development of novel biotechnology and preclinical projects.

 Publications

year authors and title journal last update
List of publications.
2019 Ana Maria Ortega-Prieto, Jessica Katy Skelton, Catherine Cherry, Marco Antonio Briones-Orta, Charlotte Alexandra Hateley, Marcus Dorner
\"\"\"Liver-on-a-Chip\"\" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection\"
published pages: , ISSN: 1940-087X, DOI: 10.3791/58333
Journal of Visualized Experiments 144 2020-02-06
2018 Ana Maria Ortega-Prieto, Catherine Cherry, Harry Gunn, Marcus Dorner
In Vivo Model Systems for Hepatitis B Virus Research
published pages: 688-702, ISSN: 2373-8227, DOI: 10.1021/acsinfecdis.8b00223
ACS Infectious Diseases 5/5 2020-02-06
2019 Michela Mazzon, Ana Ortega-Prieto, Douglas Imrie, Christin Luft, Lena Hess, Stephanie Czieso, Joe Grove, Jessica Skelton, Laura Farleigh, Joachim Bugert, Edward Wright, Nigel Temperton, Richard Angell, Sally Oxenford, Michael Jacobs, Robin Ketteler, Marcus Dorner, Mark Marsh
Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry
published pages: 176, ISSN: 1999-4915, DOI: 10.3390/v11020176
Viruses 11/2 2020-02-06
2019 Jessica Katy Skelton, Ana Maria Ortega-Prieto, Steve Kaye, Jose Manuel Jimenez-Guardeño, Jane Turner, Michael H. Malim, Greg J. Towers, Marcus Dorner
Kinetics of Early Innate Immune Activation during HIV-1 Infection of Humanized Mice
published pages: , ISSN: 0022-538X, DOI: 10.1128/JVI.02123-18
Journal of Virology 93/11 2020-02-06
2019 Antonia Alexandra Evripioti, Ana Maria Ortega-Prieto, Jessica Katy Skelton, Quentin Bazot, Marcus Dorner
Phosphodiesterase-induced cAMP degradation restricts hepatitis B virus infection
published pages: 20180292, ISSN: 0962-8436, DOI: 10.1098/rstb.2018.0292
Philosophical Transactions of the Royal Society B: Biological Sciences 374/1773 2020-02-06
2017 Ortega-Prieto AM Dorner M
Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection
published pages: 24, ISSN: 2076-393X, DOI: 10.3390/vaccines5030024
Vaccines 5/3 2019-10-03
2018 Skelton JK, Ortega-Prieto AM, Dorner M
A Hitchhiker\'s Guide to Humanized Mice: new pathways to studying viral infections
published pages: , ISSN: 1365-2567, DOI: 10.1111/imm.12906
Immunology 2019-10-03
2018 Marcus Dorner, Ype P. de Jong
Modeling Unique Patients in Humanized Mice: Toward a Curative Strategy for HIV
published pages: , ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2018.01.003
Molecular Therapy 2019-10-03
2018 C. J. Reynolds, O. M. Suleyman, A. M. Ortega-Prieto, J. K. Skelton, P. Bonnesoeur, A. Blohm, V. Carregaro, J. S. Silva, E. A. James, B. Maillère, M. Dorner, R. J. Boyton, D. M. Altmann
T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-18781-1
Scientific Reports 8/1 2019-10-03
2018 Ortega-Prieto AM Skelton JK Wai SN Large E Lussignol M Vizcay-Barrena G Hughes D Fleck RA Thursz M Catanese MT Dorner M
3D microfluidic liver cultures as physiological preclinical tool for hepatitis B virus infection
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-02969-8
Nature Communications 2019-10-03

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