Transcriptomics

Dataset Information

304

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


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 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 latency. mRNA profiles of sorted, pure antigen presenting cells including, CD1c+ myleoid dendirtic cells (mDC), SLAN+ mDC, CD14+ monocytes and plasmacytoid DC (pDC), were generated using next generation sequencing in triplicate, using Illumina Illumina Hiseq 2000.

ORGANISM(S): Homo sapiens  

SUBMITTER: David Richard Powell   Paul U Cameron  David R Powell  Nitasha Kumar 

PROVIDER: E-GEOD-70106 | ArrayExpress | 2015-12-23

SECONDARY ACCESSION(S): GSE70106SRP059735PRJNA287649

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications

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

Kumar Nitasha A NA   Cheong Karey K   Powell David R DR   da Fonseca Pereira Candida C   Anderson Jenny J   Evans Vanessa A VA   Lewin Sharon R SR   Cameron Paul U PU  

Retrovirology 20150911


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 wh  ...[more]

Similar Datasets

2015-01-01 | S-EPMC4567795 | BioStudies
2014-11-01 | E-GEOD-52344 | ArrayExpress
1000-01-01 | S-EPMC3855553 | BioStudies
1000-01-01 | S-EPMC4934909 | BioStudies
1000-01-01 | S-EPMC3640963 | BioStudies
2018-01-01 | S-EPMC6103814 | BioStudies
1000-01-01 | S-EPMC3508089 | BioStudies
2014-12-17 | E-GEOD-54480 | ArrayExpress
2012-01-01 | S-EPMC3308909 | BioStudies
2014-10-22 | E-GEOD-56744 | ArrayExpress