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Equipe 1: Immunité et Immunogénétique anti-virale et vaccinale (I2V2) - Immunité et infection
UMR S 945 INSERM-CNRS

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  • 6 équipes
  • 15 enseignants chercheurs
  • 12 chercheurs
  • 20 doctorants
  • 11 post-doctorants

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Groupe Ioannis Theodorou

The sub-group "Immunogenetics of chronic viral Infections" is coordinated by Dr Ioannis Theodorou with a 10 years experience on Immunogenetics studies of MHC or chemokine/chemokine receptors genes influence on the HIV infection in national and international cohorts of HIV-infected patients. Both groups collaborate together particularly on the role of the MHC alleles in the immune control of viruses.. The influence of the host’s genetic background in HIV infection has been first studied by the group through candidate gene approaches where the role of natural variants of Immune Response or HIV-interfering human genes, has been studied in cohorts of HIV infected patients either with extreme phenotypes (Long Term Non Progressors or Rapid Progressors) or with a known seroconversion date. Genotype distributions were compared among patients with different disease free survival. Availability of haplotype maps of the human genome and genotyping instruments analyzing at least several hundreds of thousands of Single Nucleotide Polymorphisms (SNPs) in one genome offers possibility to perform association studies after a whole genome scan without focusing on a candidate gene and therefore discover genomic regions without any a priori assumption about the function of the genes that lie in the region. The group has conducted several Genome wide Associations Studies (GWAS) using this approach in cohorts of patients already studied in the last ten years, to find new genomic regions influencing HIV disease. with success : in most cases the genetic background of a phenotype found both genes known to be involved in these diseases but also genes with an unknown function. Those cohorts have previously been genotyped for HIV disease modifying allelic variants such as CCR5 D32 and HLA; and present several phenotypes of HIV disease: ALT, PRIMO and SEROCO national cohorts, that enrolled Long Term Non Progressors, and patients with a known date of seroconverion respectively, all mounted in the pre HAART era providing opportunities to make genotype-phenotype correlations in a context of natural evolution of HIV disease or the search for genotypes influencing early viral load, one of the best surrogate markers for disease progression. The same approach is used in cohorts of patients with acute or chronic HCV disease and try to find genomic regions that influence either spontaneous clearance of the virus or genomic regions influencing the rapid development of portal fibrosis.

Another perspective of the Immunogenetics group concerns the analysis of gene expression profiles in leucocytes of patients harboring either protective or deleterious genotypes for HIV disease progression, especially for genomic regions with unknown function, in collaboration with the B Autran/G Carcelain’s subgroup.

 Theodorou’s responsibility of the ANRS genomics platform (ILLUMINA genotyping platform) provides a unique opportunity to develop large, competitive human-genome wide analysis of large cohorts, replacing the prior gene candidate approach.