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

Research output: Contribution to journalArticleResearchpeer-review

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., ... 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
Kumar, Nitasha A. ; Cheong, Karey ; Powell, David R. ; da Fonseca Pereira, Candida ; Anderson, Jenny ; Evans, Vanessa A. ; Lewin, Sharon R. ; Cameron, Paul U. / The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells. In: Retrovirology. 2015 ; Vol. 12, No. 76. pp. 1-16.
@article{976aead6465546f486539652776bc4a3,
title = "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 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.",
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",
author = "Kumar, {Nitasha A.} and Karey Cheong and Powell, {David R.} and {da Fonseca Pereira}, Candida and Jenny Anderson and Evans, {Vanessa A.} and Lewin, {Sharon R.} and Cameron, {Paul U.}",
year = "2015",
month = "9",
day = "11",
doi = "10.1186/s12977-015-0204-2",
language = "English",
volume = "12",
pages = "1--16",
journal = "Retrovirology",
issn = "1742-4690",
publisher = "Springer-Verlag London Ltd.",
number = "76",

}

Kumar, NA, Cheong, K, Powell, DR, da Fonseca Pereira, C, Anderson, J, Evans, VA, Lewin, SR & Cameron, PU 2015, 'The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells' Retrovirology, vol. 12, no. 76, 76, pp. 1-16. https://doi.org/10.1186/s12977-015-0204-2

The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells. / Kumar, Nitasha A.; Cheong, Karey; Powell, David R.; da Fonseca Pereira, Candida; Anderson, Jenny; Evans, Vanessa A.; Lewin, Sharon R.; Cameron, Paul U.

In: Retrovirology, Vol. 12, No. 76, 76, 11.09.2015, p. 1-16.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4+ T-cells

AU - Kumar, Nitasha A.

AU - Cheong, Karey

AU - Powell, David R.

AU - da Fonseca Pereira, Candida

AU - Anderson, Jenny

AU - Evans, Vanessa A.

AU - Lewin, Sharon R.

AU - Cameron, Paul U.

PY - 2015/9/11

Y1 - 2015/9/11

N2 - 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.

AB - 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.

KW - Antigen presenting cells

KW - APC

KW - B-cells

KW - Dendritic cells

KW - HIV Latency

KW - Latency induction

KW - Monocytes

KW - Post-integration latency

KW - Resting CD4<sup>+</sup> T-cells

KW - Viral reservoir

UR - http://www.scopus.com/inward/record.url?scp=84941285227&partnerID=8YFLogxK

U2 - 10.1186/s12977-015-0204-2

DO - 10.1186/s12977-015-0204-2

M3 - Article

VL - 12

SP - 1

EP - 16

JO - Retrovirology

JF - Retrovirology

SN - 1742-4690

IS - 76

M1 - 76

ER -