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

36 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

Cite this

Evans, V. A., Kumar, N., Filali, A., Procopio, F. A., Yegorov, O., Goulet, J-P., ... Lewin, S. R. (2013). Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells. PLoS Pathogens, 9(12 (Art. No.: e1003799)), 1 - 14. https://doi.org/10.1371/journal.ppat.1003799
Evans, Vanessa Anne ; Kumar, Nitasha ; Filali, Ali ; Procopio, Francesco A ; Yegorov, Oleg ; Goulet, Jean-Philippe ; Saleh, Suha Mahdi ; Haddad, Elias K ; Pereira, Candida da Fonseca ; Ellenberg, Paula Clarisa ; Sekaly, Rafick-Pierre ; Cameron, Paul Urquhart ; Lewin, Sharon Ruth. / Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells. In: PLoS Pathogens. 2013 ; Vol. 9, No. 12 (Art. No.: e1003799). pp. 1 - 14.
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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.",
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Evans, VA, Kumar, N, Filali, A, Procopio, FA, Yegorov, O, Goulet, J-P, Saleh, SM, Haddad, EK, Pereira, CDF, Ellenberg, PC, Sekaly, R-P, Cameron, PU & Lewin, SR 2013, 'Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells', PLoS Pathogens, vol. 9, no. 12 (Art. No.: e1003799), pp. 1 - 14. https://doi.org/10.1371/journal.ppat.1003799

Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells. / Evans, Vanessa Anne; Kumar, Nitasha; Filali, Ali; Procopio, Francesco A; Yegorov, Oleg; Goulet, Jean-Philippe; Saleh, Suha Mahdi; Haddad, Elias K; Pereira, Candida da Fonseca; Ellenberg, Paula Clarisa; Sekaly, Rafick-Pierre; Cameron, Paul Urquhart; Lewin, Sharon Ruth.

In: PLoS Pathogens, Vol. 9, No. 12 (Art. No.: e1003799), 2013, p. 1 - 14.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells

AU - Evans, Vanessa Anne

AU - Kumar, Nitasha

AU - Filali, Ali

AU - Procopio, Francesco A

AU - Yegorov, Oleg

AU - Goulet, Jean-Philippe

AU - Saleh, Suha Mahdi

AU - Haddad, Elias K

AU - Pereira, Candida da Fonseca

AU - Ellenberg, Paula Clarisa

AU - Sekaly, Rafick-Pierre

AU - Cameron, Paul Urquhart

AU - Lewin, Sharon Ruth

PY - 2013

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AB - 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.

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Evans VA, Kumar N, Filali A, Procopio FA, Yegorov O, Goulet J-P et al. Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells. PLoS Pathogens. 2013;9(12 (Art. No.: e1003799)):1 - 14. https://doi.org/10.1371/journal.ppat.1003799