HIV INNATE IMMUNITY

Toward an HIV-1 vaccine: Molecular mechanisms regulating the cryptic innate immune response to HIV-1

Coordinatore	INSTITUT CURIE    more  Organization address address: 26, rue d'Ulm city: PARIS postcode: 75248 contact info Titolo: Ms. Nome: Corinne Cognome: Cumin Email: send email Telefono: +33 1 56 24 66 20 Fax: +33 1 56 24 66 27
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-RG
Funding Scheme	MC-IRG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-10-01   -   2014-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT CURIE  Organization address address: 26, rue d'Ulm city: PARIS postcode: 75248 contact info Titolo: Ms. Nome: Corinne Cognome: Cumin Email: send email Telefono: +33 1 56 24 66 20 Fax: +33 1 56 24 66 27	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Our goal is to understand the innate immune response to HIV-1. We have found that a cryptic innate immune response to HIV-1 exists in dendritic cells (DC). This response is normally inactive because HIV-1 is unable to infect DC. We have used the Vpx protein found in other lentiviruses to render DC susceptible to HIV-1 infection. The resulting innate response to HIV-1 requires an interaction between de novo synthesized Capsid and cellular Cyclophilin A. This interaction leads to the IRF-3-dependant production of type-I interferon and the activation of antigen-specific T cells. This study will aim at understanding the molecular mechanisms controlling this response. In Aim 1, we will determine the host and viral factors implicated in the innate response to HIV-1. At the host level, we will evaluate a panel of candidate genes using a novel RNAi strategy using shRNA vectors in DC. At the viral level, we will determine the minimal viral elements required for triggering the response. In Aim 2, we will identify novel regulators of the innate immune response in human DC, including the DC-specific HIV-1 innate sensor. Using a DC cDNA library, we will screen for inducers of type-I interferon in cell lines. This library will also be used to identify the Vpx-sensitive HIV-restriction factor in human DC. The cryptic nature of the innate response to HIV-1 may explain in part the failure of the immune system to control HIV-1 in the vast majority of infected individuals, as well as the failure of current vaccine strategies. This study will provide a novel understanding of the molecular mechanisms responsible for innate immune responses, and may provide new immunological strategies for controlling HIV-1 infection.'