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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 my...

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Detalles Bibliográficos
Autores principales: Evans, Vanessa A., Kumar, Nitasha, Filali, Ali, Procopio, Francesco A., Yegorov, Oleg, Goulet, Jean-Philippe, Saleh, Suha, Haddad, Elias K., da Fonseca Pereira, Candida, Ellenberg, Paula C., Sekaly, Rafick-Pierre, Cameron, Paul U., Lewin, Sharon R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855553/
https://www.ncbi.nlm.nih.gov/pubmed/24339779
http://dx.doi.org/10.1371/journal.ppat.1003799
Descripción
Sumario: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.