PLoS Pathogens | |
Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4+ T Cells | |
Sharon R. Lewin1  Candida da Fonseca Pereira1  Nitasha Kumar1  Ali Filali2  Elias K. Haddad2  Vanessa A. Evans2  Paul U. Cameron2  Rafick-Pierre Sekaly3  Suha Saleh3  Jean-Philippe Goulet4  Francesco A. Procopio4  Oleg Yegorov4  Paula C. Ellenberg4  | |
[1] Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia;Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia;Laboratoire d'immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada;VGTI-Florida, Port St. Lucie, Florida, United States of America | |
关键词: T cells; HIV; Viral persistence; latency; Gene expression; Memory T cells; HIV infections; Blood; Dendritic cells; | |
DOI : 10.1371/journal.ppat.1003799 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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