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Status |
Public on Nov 01, 2014 |
Title |
Myeloid Dendritic Cells Induce HIV-1 Latency in Non-Proliferating CD4+ T Cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Latently infected resting CD4+ T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4+ T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4+ T cells. Gene expression in non-proliferating CD4+ T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4+ T cells, which is predominantly mediated through signalling during DC-T cell contact.
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Overall design |
Resting (CD69-CD25-HLA-DR-) CD4+ T cells were enriched from the blood of 4 normal donors by magnetic bead depletion and labelled with the proliferation dye SNARF. SNARFhiEGFP- CD4+ T cells cultured with (+DC) or without syngeneic bulk DC (lin-HLA-DR+), in the presence (HIV T) or absence (Mock T) of HIV, were sorted 5 days following infection with NL(AD8)-nef/EGFP (MOI 5).Culture media was supplemented with 10ng/mL of IL-7. The gene expression profile of the 4 cell populations: 1. HIV T (+DC); 2. Mock T (+DC); 3. HIV T; and 4. Mock T, was determined.
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Contributor(s) |
Vanessa AE, Filali-Mouhim A, Procopio FA, Yegorov O, Goulet JP, Saleh S, Haddad EK, Sekaly RP, Cameron PU, Lewin SR, Pan L, Cameron M, Wilkinson PA |
Citation missing |
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Submission date |
Nov 13, 2013 |
Last update date |
Mar 20, 2017 |
Contact name |
Peter A Wilkinson |
Organization name |
Case Western Reserve University
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Department |
Pathology / Systems Biology & Bioinformatics
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Street address |
2103 Cornell Road
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City |
Cleveland |
State/province |
Ohio |
ZIP/Postal code |
44120 |
Country |
USA |
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Platforms (1) |
GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
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Samples (22)
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Relations |
BioProject |
PRJNA227454 |