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

• Andreia J Amaral ^[1] ; Jorge Andrade ^[1] ; Russell B Foxall ^[1] ; Paula Matoso ^[1] ; Ana M Matos ^[1] ; Rui S Soares ^[1] ; Cheila Rocha ^[1] ; Christian G Ramos ^[1] ; Rita Tendeiro ^[1] ; Ana Serra-Caetano ^[1] ; José A Guerra-Assunção ^[2] ; Mariana Santa-Marta ^[1] ; João Gonçalves ^[1] ; Margarida Gama-Carvalho ^[1] ; Ana E Sousa ^[1]
  1. [1] Universidade de Lisboa

     Universidade de Lisboa

     Socorro, Portugal

     
  2. [2] University College London

     University College London

     Reino Unido

     
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 3, 2017, págs. 346-360
• Idioma: inglés
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• Resumen

  • 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