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Viruses 2018, 10(1), 13; https://doi.org/10.3390/v10010013

Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells

1
Institut de recherches cliniques de Montréal, Montreal, QC H2W 1R7, Canada
2
Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, QC H3T 1J4, Canada
*
Author to whom correspondence should be addressed.
Received: 21 November 2017 / Revised: 18 December 2017 / Accepted: 28 December 2017 / Published: 30 December 2017
(This article belongs to the Special Issue Homage to Mark Wainberg)
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Abstract

Human immunodeficiency virus type-1 (HIV-1) infection of monocyte/macrophages is modulated by the levels of entry receptors cluster of differentiation 4 (CD4) and C-C chemokine receptor type 5 (CCR5), as well as by host antiviral restriction factors, which mediate several post-entry blocks. We recently identified two microRNAs, miR-221 and miR-222, which limit HIV-1 entry during infection of monocyte-derived macrophages (MDMs) by down-regulating CD4 expression. Interestingly, CD4 is also down-regulated during the differentiation of monocytes into macrophages. In this study, we compared microRNA expression profiles in primary monocytes and macrophages by RNAseq and found that miR-221/miR-222 are enhanced in macrophages. We took advantage of the monocytic THP-1 cell line that, once differentiated, is poorly susceptible to HIV-1. Accordingly, we found that CD4 levels are very low in THP-1 differentiated cells and that this down-regulation of the virus receptor is the result of miR-221/miR-222 up-regulation during differentiation. We thus established a THP-1 cell line stably expressing a modified CD4 (THP-1-CD4R) that is not modulated by miR-221/miR-222. We show that in contrast to parental THP-1, this line is productively infected by HIV-1 following differentiation, sustaining efficient HIV-1 CD4-dependent replication and spread. This new THP-1-CD4R cell line represents a useful tool for the study of HIV-1-macrophage interactions particularly in contexts where spreading of viral infection is necessary. View Full-Text
Keywords: microRNA; miR-221; miR-222; THP-1 cell line; macrophage; monocyte; cluster of differentiation 4 (CD4); RNAseq; human immunodeficiency virus type-1 (HIV-1) microRNA; miR-221; miR-222; THP-1 cell line; macrophage; monocyte; cluster of differentiation 4 (CD4); RNAseq; human immunodeficiency virus type-1 (HIV-1)
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Lodge, R.; Gilmore, J.C.; Ferreira Barbosa, J.A.; Lombard-Vadnais, F.; Cohen, É.A. Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells. Viruses 2018, 10, 13.

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