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

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

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
2
University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal.
3
Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, UK.
4
Research Institute for Medicines (iMed ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
5
University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal mhcarvalho@ciencias.ulisboa.pt asousa@medicina.ulisboa.pt.
6
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal mhcarvalho@ciencias.ulisboa.pt asousa@medicina.ulisboa.pt.

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

PMID:
27993935
PMCID:
PMC5286376
DOI:
10.15252/embj.201694335
[Indexed for MEDLINE]
Free PMC Article

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