Publications & Reports

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

Evans VA, Kumar N, Filali A, Procopio FA, Yegorov O, Goulet JP, Saleh S, Haddad EK, da Fonseca Pereira C, Ellenberg PC, Sekaly RP, Cameron PU, Lewin SR
Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia ; Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.

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-kappaB 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.

Publication

  • Journal: PLoS Pathogens
  • Published: 01/12/2013
  • Volume: 9
  • Issue: 12
  • Pagination: e1003799

Health Issue

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