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

人类幼稚 CD4 T 细胞的 miRNA 分析将 miR-34c-5p 与细胞活化和 HIV 复制联系起来

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作者:Andreia J Amaral, Jorge Andrade, Russell B Foxall, Paula Matoso, Ana M Matos, Rui S Soares, Cheila Rocha, Christian G Ramos, Rita Tendeiro, Ana Serra-Caetano, José A Guerra-Assunção, Mariana Santa-Marta, João Gonçalves, Margarida Gama-Carvalho, Ana E Sousa

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.

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