Microarray data on gene modulation by HIV-1 in immune cells: 2000-2006.
Here, we review 34 HIV microarray studies in human immune cells over the period of 2000-March 2006 with emphasis on analytical approaches used and conceptual advances on HIV modulation of target cells (CD4 T cell, macrophage) and nontargets such as NK cell, B cell, and dendritic cell subsets. Results to date address advances on gene modulation associated with immune dysregulation, susceptibility to apoptosis, virus replication, and viral persistence following in vitro or in vivo infection/exposure to HIV-1 virus or HIV-1 accessory proteins. In addition to gene modulation associated with known functional correlates of HIV infection and replication (e.g., T cell apoptosis), microarray data have yielded novel, potential mechanisms of HIV-mediated pathogenesis such as modulation of cholesterol biosynthetic genes in CD4 T cells (relevant to virus replication and infectivity) and modulation of proteasomes and histone deacetylases in chronically infected cell lines (relevant to virus latency). Intrinsic challenges in summarizing gene modulation studies remain in development of sound approaches for comparing data obtained using different platforms and analytical tools, deriving unifying concepts to distil the large volumes of data collected, and the necessity to impose a focus for validation on a small fraction of genes. Notwithstanding these challenges, the field overall continues to demonstrate progress in expanding the pool of target genes validated to date in in vitro and in vivo datasets and understanding the functional correlates of gene modulation to HIV-1 pathogenesis in vivo.
Giri
Malavika S
MS
HIV Immunopathogenesis Laboratory, Wistar Institute, 3601 Spruce St., Room 480, Philadelphia, PA 19104, USA.
Nebozhyn
Michael
M
Showe
Louise
L
Montaner
Luis J
LJ
D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007962:Leukocytes / Q000276:immunology* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014779:Virus Replication / Q000276:immunology