Projects per year
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 naive, 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-?B 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.
Original language | English |
---|---|
Pages (from-to) | 1 - 14 |
Number of pages | 14 |
Journal | PLoS Pathogens |
Volume | 9 |
Issue number | 12 (Art. No.: e1003799) |
DOIs | |
Publication status | Published - 2013 |
Projects
- 1 Finished
-
DARE: Delaney AIDS Research Enterprise to Find a Cure
Lewin, S. & Cameron, P.
National Institutes of Health (United States)
8/07/11 → 30/08/14
Project: Research