Journal article
Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4(+) T Cells
PLoS pathogens, v 9(12), pp 1-14
01 Dec 2013
PMID: 24339779
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 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-kappa 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.
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Details
- Title
- Myeloid Dendritic Cells Induce HIV-1 Latency in Non-proliferating CD4(+) T Cells
- Creators
- Vanessa A. Evans - Burnet InstituteNitasha Kumar - Monash UniversityAli Filali - Vaccine & Gene Therapy Institute of FloridaFrancesco A. Procopio - Vaccine & Gene Therapy Institute of FloridaOleg Yegorov - Vaccine & Gene Therapy Institute of FloridaJean-Philippe Goulet - Centre Hospitalier de l’Université de MontréalSuha Saleh - Burnet InstituteElias K. Haddad - Vaccine & Gene Therapy Institute of FloridaCandida da Fonseca Pereira - Monash UniversityPaula C. Ellenberg - Burnet InstituteRafick-Pierre Sekaly - Centre Hospitalier de l’Université de MontréalPaul U. Cameron - Burnet InstituteSharon R. Lewin - Burnet Institute
- Publication Details
- PLoS pathogens, v 9(12), pp 1-14
- Publisher
- Public Library Science
- Number of pages
- 14
- Grant note
- 108023; 108237-51-RGRL / American Foundation for AIDS Research (amfAR) APP1041795 / National Health and Medical Research Council (NHMRC) of Australia U19 AI096109 / National Institutes of Health Delaney AIDS Research Enterprise (DARE) UM1AI126611; R56AI095073; U19AI096109 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000330535400033
- Scopus ID
- 2-s2.0-84892846389
- Other Identifier
- 991020099211204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Parasitology
- Virology