Circulating Monocytes in HIV-1-Infected Viremic Subjects Exhibit an Antiapoptosis Gene Signature and Virus- and Host-Mediated Apoptosis Resistance
| Autor: | Andrea D. Raymond, Shenoa Creer, Bethsebah Gekonge, Ronald G. Collman, Malavika S. Giri, Jane Shull, Louise C. Showe, Karam Mounzer, Aidan Hancock, Calen Nicols, Guido Silvestri, Luis J. Montaner, Malik Yousef, Jay Kostman, Michael Nebozyhn, Andrea S. Foulkes |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Chemokine Receptors CCR5 CD40 Ligand Immunology Apoptosis HIV Infections Monocytes Article Immune system medicine Cluster Analysis Humans Immunology and Allergy Macrophage Viremia Extracellular Signal-Regulated MAP Kinases Oligonucleotide Array Sequence Analysis CD40 biology Caspase 3 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Gene Expression Profiling Monocyte Middle Aged Gene signature Gene expression profiling medicine.anatomical_structure Viral replication HIV-1 biology.protein Female Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | The Journal of Immunology. 182:4459-4470 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0801450 |
| Popis: | Mechanisms that may allow circulating monocytes to persist as CD4 T cells diminish in HIV-1 infection have not been investigated. We have characterized steady-state gene expression signatures in circulating monocytes from HIV-infected subjects and have identified a stable antiapoptosis gene signature comprised of 38 genes associated with p53, CD40L, TNF, and MAPK signaling networks. The significance of this gene signature is indicated by our demonstration of cadmium chloride- or Fas ligand-induced apoptosis resistance in circulating monocytes in contrast to increasing apoptosis in CD4 T cells from the same infected subjects. As potential mechanisms in vivo, we show that monocyte CCR5 binding by HIV-1 virus or agonist chemokines serves as independent viral and host modulators resulting in increased monocyte apoptosis resistance in vitro. We also show evidence for concordance between circulating monocyte apoptosis-related gene expression in HIV-1 infection in vivo and available datasets following viral infection or envelope exposure in monocyte-derived macrophages in vitro. The identification of in vivo gene expression associated with monocyte resistance to apoptosis is of relevance to AIDS pathogenesis since it would contribute to: 1) maintaining viability of infection targets and long-term reservoirs of HIV-1 infection in the monocyte/macrophage populations, and 2) protecting a cell subset critical to host survival despite sustained high viral replication. |
| Databáze: | OpenAIRE |
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