TY - JOUR
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
Y1 - 2013
N2 - 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.
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.
UR - http://www.plospathogens.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1003799&representation=PDF
U2 - 10.1371/journal.ppat.1003799
DO - 10.1371/journal.ppat.1003799
M3 - Article
C2 - 24339779
VL - 9
SP - 1
EP - 14
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 12 (Art. No.: e1003799)
ER -