title: miR-146a controls CXCR4 expression in a pathway that involves PLZF and can be used to inhibit HIV-1 infection of CD4(+) T lymphocytes.
abstract: MicroRNA miR-146a and PLZF are reported as major players in the control of hematopoiesis, immune function and cancer. PLZF is described as a miR-146a repressor, whereas CXCR4 and TRAF6 were identified as miR-146a direct targets in different cell types. CXCR4 is a co-receptor of CD4 molecule that facilitates HIV-1 entry into T lymphocytes and myeloid cells, whereas TRAF6 is involved in immune response. Thus, the role of miR-146a in HIV-1 infection is currently being thoroughly investigated. In this study, we found that PLZF mediates suppression of miR-146a to control increases of CXCR4 and TRAF6 protein levels in human primary CD4(+) T lymphocytes. We show that miR-146a upregulation by AMD3100 treatment or PLZF silencing, decreases CXCR4 protein expression and prevents HIV-1 infection of leukemic monocytic cell line and CD4(+) T lymphocytes. Our findings improve the prospects of developing new therapeutic strategies to prevent HIV-1 entry via CXCR4 by using the PLZF/miR-146a axis.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Quaranta
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Olivetta
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Spinello
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Paolillo
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy; Department of Science, University Roma Tre, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Arenaccio
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Federico
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: catherine.labbaye@iss.it.
authors.forename: Catherine
authors.initials: C
authors.lastname: Labbaye
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D015728:Receptors, HIV / Q000096:biosynthesis*; D053586:Virus Internalization
chemical_list: C527276:CXCR4 protein, human; D051741:Kruppel-Like Transcription Factors; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D019718:Receptors, CXCR4; D015728:Receptors, HIV; C092037:ZBTB16 protein, human
keywords: CD4(+) T lymphocytes; CXCR4; HIV-1; PLZF; U937 cells.; miR-146a