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SENTINEL SIGNED

HIV-1 sensing and signaling in dendritic cells

Total Cost €

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EC-Contrib. €

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Partnership

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Project "SENTINEL" data sheet

The following table provides information about the project.

Coordinator
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM 

Organization address
address: MEIBERGDREEF 15
city: AMSTERDAM
postcode: 1105AZ
website: www.amc.nl

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 Netherlands [NL]
 Total cost 2˙499˙156 €
 EC max contribution 2˙499˙156 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-10-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM NL (AMSTERDAM) coordinator 2˙499˙156.00

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 Project objective

HIV-1 is a major global health problem with over 2 million new infections every year, and although antiretroviral therapy is effective, chronic infected patients suffer from severe co-morbidities due to immune dysfunction. With the proposed SENTINEL project, I aim to identify novel strategies to enhance innate antiviral immunity to HIV-1 to limit establishment and progression of chronic disease. Our novel data strongly suggest that induction of antiviral innate immune responses in dendritic cell subsets delays disease progression and improves survival in chronic HIV-1-infected patients. Current paradigm suggests that HIV-1 evades innate sensing in dendritic cells and that this underlies immune dysfunction. However, our innovative data demonstrate that HIV-1 actively suppresses a novel innate sensing mechanism and antagonizing this HIV-1 suppression by drugs strongly enhanced antiviral immunity. Strikingly, we identified a gene polymorphism in a component of the novel HIV-1 sensing machinery, rendering the pathway insensitive to HIV-1 suppression; this polymorphism is associated with delayed disease progression and improved survival in HIV-1 patients from the Amsterdam Cohort Studies. Thus, I hypothesize that therapies counteracting the suppression by HIV-1 will enhance antiviral immunity and restore immune dysfunction in chronic patients. Within this SENTINEL project, novel targets for HIV-1 therapy will be identified. As we identified proto-oncogenes involved in the suppression of innate immune responses by HIV-1, we will also screen clinically approved anti-cancer drugs as novel therapies to enhance the innate immune responses to HIV-1. Our exciting data strongly underscore the innovation and feasibility of the project. The unique expertise of my group in elucidating complex mechanisms that shape immunity, our innovative ex vivo human tissue infection models and cohort studies will be crucial in the proposed research and paramount to its success.

 Publications

year authors and title journal last update
List of publications.
2017 Joris K. Sprokholt, Marieke H. Heineke, Tanja M. Kaptein, John L. van Hamme, Teunis B. H. Geijtenbeek
DCs facilitate B cell responses against microbial DNA via DC-SIGN
published pages: e0185580, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0185580
PLOS ONE 12/10 2019-09-02
2017 Joris K. Sprokholt, Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek
RIG-I–like Receptor Triggering by Dengue Virus Drives Dendritic Cell Immune Activation and T H 1 Differentiation
published pages: 4764-4771, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1602121
The Journal of Immunology 198/12 2019-09-02
2017 Nina Hertoghs, Teunis B.H. Geijtenbeek, Carla M.S. Ribeiro
Interplay between HIV-1 innate sensing and restriction in mucosal dendritic cells: balancing defense and viral transmission
published pages: 112-119, ISSN: 1879-6257, DOI: 10.1016/j.coviro.2017.01.001
Current Opinion in Virology 22 2019-09-02
2017 Joris K. Sprokholt, Tanja M. Kaptein, John L. van Hamme, Ronald J. Overmars, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek
RIG-I-like receptor activation by dengue virus drives follicular T helper cell formation and antibody production
published pages: e1006738, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006738
PLOS Pathogens 13/11 2019-09-02
2016 Teunis B. H. Geijtenbeek, Sonja I. Gringhuis
C-type lectin receptors in the control of T helper cell differentiation
published pages: 433-448, ISSN: 1474-1733, DOI: 10.1038/nri.2016.55
Nature Reviews Immunology 16/7 2019-09-02
2018 Marta Bermejo-Jambrina, Julia Eder, Leanne C. Helgers, Nina Hertoghs, Bernadien M. Nijmeijer, Melissa Stunnenberg, Teunis B. H. Geijtenbeek
C-Type Lectin Receptors in Antiviral Immunity and Viral Escape
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.00590
Frontiers in Immunology 9 2019-09-02
2016 Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3
published pages: 225-235, ISSN: 1529-2908, DOI: 10.1038/ni.3647
Nature Immunology 18/2 2019-09-02
2018 Melissa Stunnenberg, Teunis B.H. Geijtenbeek, Sonja I. Gringhuis
DDX3 in HIV-1 infection and sensing: A paradox
published pages: 32-39, ISSN: 1359-6101, DOI: 10.1016/j.cytogfr.2018.03.001
Cytokine & Growth Factor Reviews 40 2019-09-02
2016 Carla M. S. Ribeiro, Ramin Sarrami-Forooshani, Laurentia C. Setiawan, Esther M. Zijlstra-Willems, John L. van Hamme, Wikky Tigchelaar, Nicole N. van der Wel, Neeltje A. Kootstra, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek
Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets
published pages: 448-452, ISSN: 0028-0836, DOI: 10.1038/nature20567
Nature 540/7633 2019-09-02

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