Microarray data on gene modulation by HIV-1 in immune cells: 2000–2006

Abstract

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.

Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

“…The impact of HIV-1 viremia on monocyte activation, gene expression (8,(18)(19)(20), and function (9-11, 13, 21, 22) is largely independent of productive monocyte infection, as only an estimated 0.03 to 0.1% of circulating monocytes harbor integrated HIV-1 DNA (11,23,24). However, exposure to viral particles and proteins, microbial products, and host products (such as cytokines) can modulate monocyte function (8,19,20,(25)(26)(27)(28) and apoptosis (18,(29)(30)(31) during disease.…”

Analysis of HIV-1 Expression Level and Sense of Transcription by High-Throughput Sequencing of the Infected Cell

“…The overlap varied from 4% in the study of circulating monocytes in HIV-infected individuals (17) to 8% in the analysis of lymphatic tissue in the setting of various stages of HIV-1 infection in vivo (29). There also was a 6% overlap with a set of validated genes curated by Giri et al (16). The final shortlist of 52 genes common between the present and one or more of the previous studies (see Fig.…”

Proteomic Studies Reveal Coordinated Changes in T-Cell Expression Patterns upon Infection with Human Immunodeficiency Virus Type 1

“…HIV-1 disturbs immune responses, changes infected cells so that it can survive and persist, and prepares the cells for production and release of new viral particles. The intracellular processes influenced by HIV infection have been the subject of intense research, including studies that focus mainly on the role of HIV-1 accessory proteins in these processes and more general studies using microarrays to detect mRNA changes in the cell (11,16,42,51). The proteome changes, however, have only recently begun to be studied in detail (9).…”