miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication

EMBO J. 2017 Feb 1;36(3):346-360. doi: 10.15252/embj.201694335. Epub 2016 Dec 19.

Abstract

Cell activation is a vital step for T-cell memory/effector differentiation as well as for productive HIV infection. To identify novel regulators of this process, we used next-generation sequencing to profile changes in microRNA expression occurring in purified human naive CD4 T cells in response to TCR stimulation and/or HIV infection. Our results demonstrate, for the first time, the transcriptional up-regulation of miR-34c-5p in response to TCR stimulation in naive CD4 T cells. The induction of this miR was further consistently found to be reduced by both HIV-1 and HIV-2 infections. Overexpression of miR-34c-5p led to changes in the expression of several genes involved in TCR signaling and cell activation, confirming its role as a novel regulator of naive CD4 T-cell activation. We additionally show that miR-34c-5p promotes HIV-1 replication, suggesting that its down-regulation during HIV infection may be part of an anti-viral host response.

Keywords: HIV‐1; HIV‐2; T‐cell activation; miR‐34c‐5p; naive CD4 T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Gene Expression Profiling
  • HIV / immunology
  • HIV / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Immune Evasion
  • Lymphocyte Activation*
  • MicroRNAs / analysis*
  • Receptors, Antigen, T-Cell / metabolism*
  • Virus Replication*

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • Receptors, Antigen, T-Cell