MiRNA Profiling of Human Naive CD4 T Cells Links MiR-34c-5p to Cell Activation and HIV Replication

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2016 Dec 21

PMID 27993935

Citations 24

Authors

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

Jose A Guerra-Assuncao

Mariana Santa-Marta

Joao Goncalves

Margarida Gama-Carvalho

Ana E Sousa

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Grossman Z, Meier-Schellersheim M, Sousa A, Victorino R, Paul W . CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause?. Nat Med. 2002; 8(4):319-23. DOI: 10.1038/nm0402-319. View

Sousa A, Carneiro J, Meier-Schellersheim M, Grossman Z, Victorino R . CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol. 2002; 169(6):3400-6. DOI: 10.4049/jimmunol.169.6.3400. View

Cannell I, Kong Y, Johnston S, Chen M, Collins H, Dobbyn H . p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication. Proc Natl Acad Sci U S A. 2010; 107(12):5375-80. PMC: 2851793. DOI: 10.1073/pnas.0910015107. View

DOrso I, Frankel A . Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex. Proc Natl Acad Sci U S A. 2009; 106(9):3101-6. PMC: 2651313. DOI: 10.1073/pnas.0900012106. View

S Soares R, Matoso P, Calado M, Sousa A . Strategies to quantify unspliced and multiply spliced mRNA expression in HIV-2 infection. J Virol Methods. 2011; 175(1):38-45. DOI: 10.1016/j.jviromet.2011.04.012. View

Chim C, Wan T, Wong K, Fung T, Drexler H, Wong K . Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms. J Transl Med. 2011; 9:197. PMC: 3283527. DOI: 10.1186/1479-5876-9-197. View

Yamane H, Paul W . Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets. Immunol Rev. 2013; 252(1):12-23. PMC: 3578301. DOI: 10.1111/imr.12032. View

He L, He X, Lim L, de Stanchina E, Xuan Z, Liang Y . A microRNA component of the p53 tumour suppressor network. Nature. 2007; 447(7148):1130-4. PMC: 4590999. DOI: 10.1038/nature05939. View

Smyth G . Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2006; 3:Article3. DOI: 10.2202/1544-6115.1027. View

10.

Tendeiro R, Foxall R, Baptista A, Pinto F, S Soares R, Cavaleiro R . PD-1 and its ligand PD-L1 are progressively up-regulated on CD4 and CD8 T-cells in HIV-2 infection irrespective of the presence of viremia. AIDS. 2012; 26(9):1065-71. DOI: 10.1097/QAD.0b013e32835374db. View

11.

Amaral A, Andrade J, Foxall R, Matoso P, Matos A, S Soares R . miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication. EMBO J. 2016; 36(3):346-360. PMC: 5286376. DOI: 10.15252/embj.201694335. View

12.

Chavez L, Calvanese V, Verdin E . HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells. PLoS Pathog. 2015; 11(6):e1004955. PMC: 4466167. DOI: 10.1371/journal.ppat.1004955. View

13.

Nunes-Cabaco H, Matoso P, Foxall R, Tendeiro R, Pires A, Carvalho T . Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes. J Virol. 2014; 89(4):2201-8. PMC: 4338895. DOI: 10.1128/JVI.03047-14. View

14.

Lu L, Gasteiger G, Yu I, Chaudhry A, Hsin J, Lu Y . A Single miRNA-mRNA Interaction Affects the Immune Response in a Context- and Cell-Type-Specific Manner. Immunity. 2015; 43(1):52-64. PMC: 4529747. DOI: 10.1016/j.immuni.2015.04.022. View

15.

Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y . Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008; 68(11):4123-32. DOI: 10.1158/0008-5472.CAN-08-0325. View

16.

Rokavec M, Li H, Jiang L, Hermeking H . The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014; 6(3):214-30. DOI: 10.1093/jmcb/mju003. View

17.

Langmead B . Aligning short sequencing reads with Bowtie. Curr Protoc Bioinformatics. 2010; Chapter 11:Unit 11.7. PMC: 3010897. DOI: 10.1002/0471250953.bi1107s32. View

18.

Thai T, Calado D, Casola S, Ansel K, Xiao C, Xue Y . Regulation of the germinal center response by microRNA-155. Science. 2007; 316(5824):604-8. DOI: 10.1126/science.1141229. View

19.

Flynt A, Lai E . Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet. 2008; 9(11):831-42. PMC: 2729318. DOI: 10.1038/nrg2455. View

20.

Montojo J, Zuberi K, Rodriguez H, Kazi F, Wright G, Donaldson S . GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics. 2010; 26(22):2927-8. PMC: 2971582. DOI: 10.1093/bioinformatics/btq562. View