Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4+ T Cells

PLoS Pathogens

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