A minority (<5%) of all HIV-1 infected individuals have been defined as long-term nonprogressors (LTNP) in that they maintain exceptionally prolonged survival in the absence of clinical symptoms and without receiving antiretroviral therapy. Several cohorts of LTNP have been identified in Europe and national networks have been formed in France and Italy to better study their particular features. GISHEAL is the first collaborative European consortium focusing on the LTNP condition with particular regard to the host genetic background and gene expression profiling and to the adaptive and innate immunological responses to the infection. A common database will be formed by merging two existing national (French, Italian) databases supplemented with additional data collected from LTNP cohorts currently followed-up in the UK and Uganda. A genome-wide approach based on screening of >100,000 single-nucleotide polymorphisms (SNPs) followed by proper validation steps will lead to the potential discovery of novel genetic polymorphisms linked to LTNP in addition to those already described. Their consequence in terms of gene expression will be studied in different populations of leukocytes (CD4, CD8, monocytes, NK and T cells) by microfluidic cards based on multi-parametric real-time PCR (TaqMan) in selected LTNP and control chronic progressors (CP). The adaptive T lymphocyte (CD4, CD8) immune responses as well as the NK cell and T cell responses to HIV will be studied in LTNP and CP. The functional consequences of the potentially novel genetic and post-genomic correlates of therapy-independent long-term non-progression in HIV infection will be also investigated in these immune cells. A multivariate analysis will allow definition of the best correlates of non-progression that could be of relevance to the general population of HIV-infected individuals.
Fields of science
- medical and health scienceshealth sciencespublic and environmental healthepidemics preventionimmunisation
- medical and health scienceshealth sciencesinfectious diseaseRNA virushiv
- natural sciencescomputer and information sciencesdatabases
- natural sciencesbiological sciencesgenetics and hereditynucleotide
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