Deep sequencing of human naive CD4 T cells identifies miR-34c-5p as a novel regulator of T cell activation and HIV replication

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 HIV infection. HIV infection had no significant impact on global miR expression in quiescent naïve CD4 T cells. We identified miR-34c-5p as a novel miR strongly induced by TCR stimulation of naïve CD4 T cells, and found that it was consistently down-regulated in response to viral infection. Over-expression of miR-34c-5p had a positive effect on HIV-1 replication. Finally, we demonstrated that miR-34c-5p alters the expression of several genes involved in TCR signaling and cell activation, identifying it as a novel regulator of naïve CD4 T cell activation potentially targeted by HIV infection.