HIVINNATE

Characterisation and Manipulation of Primate Lentiviral Interactions with Innate Immunity

 Coordinatore UNIVERSITY COLLEGE LONDON 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 2˙499˙643 €
 EC contributo 2˙499˙643 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-ADG
 Funding Scheme ERC-AG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-02-01   -   2019-01-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Ms.
Nome: Malgorzata
Cognome: Kielbasa
Email: send email
Telefono: +44 20 3108 3064
Fax: +44 20 78132849

UK (LONDON) hostInstitution 2˙499˙643.00
2    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Prof.
Nome: Gregory John
Cognome: Towers
Email: send email
Telefono: +44 2 03108 2112
Fax: +44 2 03108 2123

UK (LONDON) hostInstitution 2˙499˙643.00

Mappa


 Word cloud

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triggering    cell    manipulating    immune    macrophages    replicates    sensors    hiv    innate    maturation    virus    molecular    interaction    interferon    potency    details    responses    immunity    primary    cells    antiviral    dc    cd   

 Obiettivo del progetto (Objective)

'Our aim is to seek detailed molecular level understanding of the interactions between HIV-1 and innate immune sensors expressed in myeloid cells. We have demonstrated that HIV-1 replicates in primary human macrophages without triggering interferon production. However, by specific mutation of HIV-1 proteins or by manipulating interaction with host cofactors we can reveal the virus to innate immune receptors and activate an antiviral response leading to secretion of soluble type 1 interferon and cessation of replication. We propose to define the sensors and the details of the antiviral pathways that are activated in macrophages using proven RNA interference techniques reading out activation of innate immune responses by measurement of secreted interferon and induction of gene expression. We have also characterised small molecules that potently inhibit HIV-1 by revealing HIV-1 to innate immune sensors. In collaboration with crystallographers and medicinal chemists we aim to improve the potency and specificity of these drugs and to use them to study the anti-HIV-1 innate immune response. DC are sentinels of innate immunity and their infection induced maturation leads to interferon production and DC dependent T cell maturation that defines the nature and potency of the immune response. We will examine the effect of triggering innate responses in DC using HIV-1 mutants/drug treated wild type virus on allogeneic responses, by measurement of T cell proliferation and function and in an ex vivo CD8 T cell killing assays using peripheral blood CD8 cells from HIV‑1 infected patients. In this way we will uncover the molecular details of HIV-1’s interaction with innate immunity and discover how the virus replicates in primary immune cells without detection. This work will make a significant technical and intellectual contribution to an important emerging scientific field focusing on understanding and manipulating the complex relationship between HIV-1 and innate immunity.'

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