mi RNA profiling of human naive CD 4 T cells links miR‐34c‐5p to cell activation and HIV replication

• Published in: The EMBO journal 2017-02, Vol.36 (3), p.346-360
• Main Authors: Amaral, Andreia J, Andrade, Jorge, Foxall, Russell B, Matoso, Paula, Matos, Ana M, Soares, Rui S, Rocha, Cheila, Ramos, Christian G, Tendeiro, Rita, Serra‐Caetano, Ana, Guerra‐Assunção, José A, Santa‐Marta, Mariana, Gonçalves, João, Gama‐Carvalho, Margarida, Sousa, Ana E
• Format: Article
• Language: English
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.201694335

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 micro RNA expression occurring in purified human naive CD 4 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 CD 4 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 CD 4 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. image miR‐34c‐5p is a novel player in TCR ‐stimulated human naive CD 4 T cells, emerging as a common link between cell activation and HIV replication. Its down‐regulation on HIV ‐1 or HIV ‐2 infection may be an anti‐viral cell response to limit HIV production. miR‐34c‐5p is a novel regulator of TCR ‐mediated naive CD 4 T‐cell activation. Small RNA ‐seq reveals stable miR levels in human naive CD 4 T cells exposed to HIV . HIV infection of TCR ‐activated naive CD 4 T cells results in miR‐34c‐5p down‐regulation. miR‐34c‐5p overexpression promotes HIV replication.