title: Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells.
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 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.
authors: Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia ; Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors: Vanessa A
authors: VA
authors: Evans
authors: Nitasha
authors: N
authors: Kumar
authors: Ali
authors: A
authors: Filali
authors: Francesco A
authors: FA
authors: Procopio
authors: Oleg
authors: O
authors: Yegorov
authors: Jean-Philippe
authors: JP
authors: Goulet
authors: Suha
authors: S
authors: Saleh
authors: Elias K
authors: EK
authors: Haddad
authors: Candida
authors: C
authors: da Fonseca Pereira
authors: Paula C
authors: PC
authors: Ellenberg
authors: Rafick-Pierre
authors: RP
authors: Sekaly
authors: Paul U
authors: PU
authors: Cameron
authors: Sharon R
authors: SR
authors: Lewin
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D046228:Microarray Analysis; D022423:Myeloid Cells / Q000502:physiology*; D059467:Transcriptome; D017735:Virus Latency / Q000235:genetics / Q000276:immunology