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

Vanessa Anne Evans, Nitasha Kumar, Ali Filali, Francesco A Procopio, Oleg Yegorov, Jean-Philippe Goulet, Suha Mahdi Saleh, Elias K Haddad, Candida da Fonseca Pereira, Paula Clarisa Ellenberg, Rafick-Pierre Sekaly, Paul Urquhart Cameron, Sharon Ruth Lewin

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

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 languageEnglish
Pages (from-to)1 - 14
Number of pages14
JournalPLoS Pathogens
Volume9
Issue number12 (Art. No.: e1003799)
DOIs
Publication statusPublished - 2013

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