Transcription profiling of human CD4+ T cells from HIV infected individuals vs. controls reveals type I interferon-mediated disruption of T cell dynamics

ABSTRACT: The mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore, we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection. Experiment Overall Design: This experiment compares the expression of CD4+ T-cells obtained from 11 HIV+ individuals with that from comparable 9 HIV- control individuals. Each individual's cells were analyzed on separate single-color chips, and the average values of both biological replicate groups were analyzed for statistical significance. Experiment Overall Design: The biological significance of up- and down-regulated probesets/genes was analyzed using the Gene Ontology annotation dataset.

ORGANISM(S): Homo sapiens

SUBMITTER: Ahmad Sedaghat 

PROVIDER: E-GEOD-9927 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress