The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells

Nitasha A. Kumar, Karey Cheong, David R. Powell, Candida da Fonseca Pereira, Jenny Anderson, Vanessa A. Evans, Sharon R. Lewin, Paul U. Cameron

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Abstract

Background: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4+ T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4+ T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4+ T-cells co-cultured with CD11c+ myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4+ T-cells, and examined potential cell interactions that may be involved using RNA-seq. Results: mDC (CD1c+), SLAN+ DC and CD14+ monocytes were most efficient in stimulating proliferation of CD4+ T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4+ T-cells following HIV-1 infection of APC-T cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4+ T-cells. Gene expression analysis, comparing the CD1c+ mDC, SLAN+ DC and CD14+ monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4+ T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). Conclusions: APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14+ monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4+ T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV-1 latency.

Original languageEnglish
Article number76
Pages (from-to)1-16
Number of pages16
JournalRetrovirology
Volume12
Issue number76
DOIs
Publication statusPublished - 11 Sep 2015

Keywords

  • Antigen presenting cells
  • APC
  • B-cells
  • Dendritic cells
  • HIV Latency
  • Latency induction
  • Monocytes
  • Post-integration latency
  • Resting CD4<sup>+</sup> T-cells
  • Viral reservoir

Cite this

Kumar, N. A., Cheong, K., Powell, D. R., da Fonseca Pereira, C., Anderson, J., Evans, V. A., Lewin, S. R., & Cameron, P. U. (2015). The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells. Retrovirology, 12(76), 1-16. [76]. https://doi.org/10.1186/s12977-015-0204-2