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Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells


Resting CD4+ T cells within lymphoid tissues are a reservoir of latent infection; however, in isolated resting CD4+ T cells, several blocks exist that restrict HIV-1 replication. We hypothesize that interactions with dendritic cells (DCs) within lymphoid tissues contribute to the establishment of latency.


SNARF-labelled resting CD4+ T cells were cultured alone or with DC for 24 prior to mock infection or infection with a CCR5-using, EGFP-reporter virus. Non-proliferating (SNARFhi) CD4+ T cells that were not productively infected (EGFP-) were purified five days post infection and: (1) latent infection was reactivated and amplified by co-culturing the sorted cells with mitogen-stimulated PBMC for five days; and (2) gene expression changes were compared in sorted non-proliferating CD4+ T cells cultured in the presence or absence of DCs with or without HIV-1 infection using oligonucleotide microarrays.


In the presence of DCs, a significant increase in the number of latently infected non-proliferating CD4+ T cells (p=0.01) was observed when compared with resting CD4+ T cells cultured alone. These cells had not entered into the cell cycle as confirmed by the lack of Ki67 expression, although 2% of the DC co-cultured cells did express the early activation marker CD69. Post-integration latency was detected in the non-proliferating CD4+ T cells following co-culture with sorted myeloid (mDC) but not plasmacytoid DC (pDC), which was confirmed using Alu-LTR PCR to detect integrated HIV-1 DNA (11,000 and <300 copies/million cells, respectively). We identified 193 genes that were differentially expressed in the latently infected non-proliferating CD4+ T cells. Observations include the induction of multiple genes associated with cell cycle arrest and the inhibition of HIV-1 transcription.


Our results suggest a possible pathway for mDC-induced latency in CD4+ T cells in which low levels of cell activation may allow for enhanced HIV-1 integration, but subsequent blocks in transcription and cell proliferation prevent progression to productive infection.

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Correspondence to VA Evans.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Evans, V., Saleh, S., Haddad, E. et al. Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells. JIAS 13 (Suppl 3), O7 (2010).

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