title: Genome-wide analysis of primary CD4+ and CD8+ T cell transcriptomes shows evidence for a network of enriched pathways associated with HIV disease.
abstract: BACKGROUND
  HIV preferentially infects CD4+ T cells, and the functional impairment and numerical decline of CD4+ and CD8+ T cells characterize HIV disease. The numerical decline of CD4+ and CD8+ T cells affects the optimal ratio between the two cell types necessary for immune regulation. Therefore, this work aimed to define the genomic basis of HIV interactions with the cellular transcriptome of both CD4+ and CD8+ T cells.
  
  
  RESULTS
  Genome-wide transcriptomes of primary CD4+ and CD8+ T cells from HIV+ patients were analyzed at different stages of HIV disease using Illumina microarray. For each cell subset, pairwise comparisons were performed and differentially expressed (DE) genes were identified (fold change >2 and B-statistic >0) followed by quantitative PCR validation. Gene ontology (GO) analysis of DE genes revealed enriched categories of complement activation, actin filament, proteasome core and proton-transporting ATPase complex. By gene set enrichment analysis (GSEA), a network of enriched pathways functionally connected by mitochondria was identified in both T cell subsets as a transcriptional signature of HIV disease progression. These pathways ranged from metabolism and energy production (TCA cycle and OXPHOS) to mitochondria meditated cell apoptosis and cell cycle dysregulation. The most unique and significant feature of our work was that the non-progressing status in HIV+ long-term non-progressors was associated with MAPK, WNT, and AKT pathways contributing to cell survival and anti-viral responses.
  
  
  CONCLUSIONS
  These data offer new comparative insights into HIV disease progression from the aspect of HIV-host interactions at the transcriptomic level, which will facilitate the understanding of the genetic basis of transcriptomic interaction of HIV in vivo and how HIV subverts the human gene machinery at the individual cell type level.
authors.affiliation: Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute, University of Sydney, Darcy Road, Westmead, NSW 2145, Australia.
authors.forename: Jing Qin
authors.initials: JQ
authors.lastname: Wu
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Dyer
authors.forename: Yee Hwa
authors.initials: YH
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018450:Disease Progression; D020869:Gene Expression Profiling; D015894:Genome, Human; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D018655:Lymphocyte Count; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017741:Survivors; D014766:Viremia / Q000276:immunology / Q000503:physiopathology / Q000821:virology
chemical_list: D011506:Proteins