Navigation path

GISHEAL


HIV/AIDS

Genetic and Immunological Studies of European and African HIV-1+ Long Term Non-Progressors
Framework programme:
6
Call:
4
Project number:
LSHP-CT-2007-037616
EC contribution:
€ 1,100,000
Duration:
24 Months
Type:
STREP
Starting date:
February 2007

Keywords: HIV-1, LTNP, Genetics, post-genomic, SNP, NK, gamma-delta, T cell, cohort, database

Summary:

A minority (<5%) of hiv-1 infected individuals maintains exceptionally prolonged survival in the absence of clinical symptoms and without antiretroviral therapy; these individuals have been defined here as long term non-progressors (ltnp).

Several cohorts of LTNP have been identified in Europe and elsewhere, and national networks have been formed in France and Italy to better study their particular features. GISHEAL is the first collaborative European consortium aimed at investigating the precise nature of the LTNP state, with particular regard to the host genetic background and gene expression profiling, and to the adaptive and innate immunological responses to the infection. After identification of LTNP by all participants, the GISHEAL common database will be prepared representing the merger of two national (French, Italian) databases together with individual data collected from the UK and Uganda. A genome-wide approach based on screening of 500,000 single-nucleotide polymorphisms (SNP) followed by validation steps, will lead to the potential discovery of novel genetic polymorphisms linked to the LTNP condition, in addition to those already described.

Their effect in terms of gene expression will be studied in different populations of peripheral blood leukocytes (CD4, CD8, monocytes, NK and γδ T cells) using a microfluidic card approach based on multi-parametric real-time PCR (TaqMan) in selected LTNP and chronic progressors (CP) as controls. The adaptive CD4 and CD8 T lymphocyte immune responses of LTNP to HIV-1 will be studied, in comparison to those of viraemic CP. In parallel, the NK cell and γδ T cell responses of LTNP and CP will be investigated. The functional consequences of the potentially novel genetic correlates of LTNP will be also investigated in these immune cells. A multivariate analysis will allow definition of the best correlates of non-progression.

[+] Read More