title: miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication.
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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal.
authors.forename: Andreia J
authors.identifier: 0000-0003-0958-5570
authors.initials: AJ
authors.lastname: Amaral
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal.
authors.forename: Jorge
authors.identifier: 0000-0002-6588-5300
authors.initials: J
authors.lastname: Andrade
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Russell B
authors.identifier: 0000-0001-9821-0708
authors.initials: RB
authors.lastname: Foxall
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Matoso
authors.affiliation: University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal.
authors.forename: Ana M
authors.identifier: 0000-0002-0160-256X
authors.initials: AM
authors.lastname: Matos
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Rui S
authors.identifier: 0000-0001-6573-5292
authors.initials: RS
authors.lastname: Soares
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Cheila
authors.identifier: 0000-0002-0148-9405
authors.initials: C
authors.lastname: Rocha
authors.affiliation: University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal.
authors.forename: Christian G
authors.identifier: 0000-0003-0970-7750
authors.initials: CG
authors.lastname: Ramos
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Tendeiro
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Serra-Caetano
authors.affiliation: Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, UK.
authors.forename: José A
authors.identifier: 0000-0001-6593-403X
authors.initials: JA
authors.lastname: Guerra-Assunção
authors.affiliation: Research Institute for Medicines (iMed ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Mariana
authors.identifier: 0000-0002-0243-4158
authors.initials: M
authors.lastname: Santa-Marta
authors.affiliation: Research Institute for Medicines (iMed ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: João
authors.identifier: 0000-0002-1245-3715
authors.initials: J
authors.lastname: Gonçalves
authors.affiliation: University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Portugal mhcarvalho@ciencias.ulisboa.pt asousa@medicina.ulisboa.pt.
authors.forename: Margarida
authors.identifier: 0000-0002-0365-6916
authors.initials: M
authors.lastname: Gama-Carvalho
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal mhcarvalho@ciencias.ulisboa.pt asousa@medicina.ulisboa.pt.
authors.forename: Ana E
authors.identifier: 0000-0002-4618-9799
authors.initials: AE
authors.lastname: Sousa
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D020869:Gene Expression Profiling; D006678:HIV / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011948:Receptors, Antigen, T-Cell
keywords: HIV‐1; HIV‐2; T‐cell activation; miR‐34c‐5p; naive CD4 T cells