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SAMPLES (202)

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Physiopathology
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User name	José Felipe Golib Dzib
Email	golib@ihes.fr
Phone / Fax number	+33(0)160926665 / +33(0)160926609
Location	I.H.E.S. (Systems Epigenomics Group) - 35 route de chartres - 91440 Bures sur Yvette, France

Scientific description

There is great interindividual variability in HIV-1 viral set point after seroconversion, some of which is known to be due to genetic differences among infected individuals. Here, our focus is on determining, genome-wide, the contribution of variable gene expression to viral control, and to relate it to genomic DNA polymorphism. RNA was extracted from purified CD4+ T-cells from 137 HIV-1 seroconverters, 16 elite controllers, and 3 healthy blood donors. Expression levels of more than 48,000 mRNA transcripts were assessed by the Human-6 v3 Expression BeadChips (Illumina). Genome-wide SNP data was generated from genomic DNA using the HumanHap550 Genotyping BeadChip (Illumina). We observed two distinct profiles with 260 genes differentially expressed depending on HIV-1 viral load. There was significant upregulation of expression of interferon stimulated genes with increasing viral load, including genes of the intrinsic antiretroviral defense. Upon successful antiretroviral treatment, the transcriptome profile of previously viremic individuals reverted to a pattern comparable to that of elite controllers and of uninfected individuals. Genome-wide evaluation of cis-acting SNPs identified genetic variants modulating expression of 190 genes. Those were compared to the genes whose expression was found associated with viral load: expression of one interferon stimulated gene, OAS1, was found to be regulated by a SNP (rs3177979, p=4.9E-12); however, we could not detect an independent association of the SNP with viral set point. Thus, this study represents the first attempt to integrate genome-wide SNP signals with genome-wide expression profiles in the search for biological correlates of HIV-1 control. It underscores the paradox of the association between increasing levels of viral load and greater expression of antiviral defense pathways. It also shows that elite controllers do not have a distinctive mRNA expression pattern in CD4+ T cells. Changes in RNA expression reflect responses to viral replication rather than a mechanism that might explain viral control

Technical description

Total RNA from 202 samples obtained from CD4 T cells from HIV infected individuals to identify associations between variation in gene expression viral set point. Samples belong to different groups as follows (Paired Untreated/treated samples: 38/38, only untreated samples: 89, successfully treated samples: 29. Eight samples from 3 healthy blood donors in replicates.

Reference

Rotger M, Dang KK, Fellay J, Heinzen EL et al. Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals. PLoS Pathog  2010 Feb 26;6(2):e1000781.

Pubmed : http://www.ncbi.nlm.nih.gov/pubmed/20195503