Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4+ T Cells

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 cd4+ t cells,which is predominantly mediated through signalling during dc-t cell contact. © 2013 evans et al.