Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells

PLoS Pathogens
Vanessa A EvansSharon R Lewin

Abstract

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. Latency was eliminated when cell-to-cell contact was prevented in the mDC-T cell co-cultures and reduced when clustering was minimised in the mDC-T cell co-cultures. Supernatants from infected mDC-T cell co-cultures did not facilitate the establishment of latency, consistent with cell-cell contact and not a soluble factor being critical for mediating latent infection of resting 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 ...Continue Reading

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Citations

Apr 25, 2014·Viruses·Amit KumarGeorges Herbein
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Methods Mentioned

BETA
flow cytometry
PCR
gene knockdown
transfection
FACS
chip
gene-array

Software Mentioned

LIMMA
Ingenuity Pathway Analysis
Bioconductor
Illumina BeadStudio
Weasel
Ingenuity Pathway Analysis ( IPA )
Graphpad Prism
Ingenuity
BeadStudio
R

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