Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells
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 recen...
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doaj-daba3da829ab4ff281c015b3f95b118a2020-11-24T21:27:50ZengMDPI AGViruses1999-49152017-12-011011310.3390/v10010013v10010013Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 CellsRobert Lodge0Julian C. Gilmore1Jérémy A. Ferreira Barbosa2Félix Lombard-Vadnais3Éric A. Cohen4Institut de recherches cliniques de Montréal, Montreal, QC H2W 1R7, CanadaInstitut de recherches cliniques de Montréal, Montreal, QC H2W 1R7, CanadaInstitut de recherches cliniques de Montréal, Montreal, QC H2W 1R7, CanadaInstitut de recherches cliniques de Montréal, Montreal, QC H2W 1R7, CanadaInstitut de recherches cliniques de Montréal, Montreal, QC H2W 1R7, CanadaHuman 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.https://www.mdpi.com/1999-4915/10/1/13microRNAmiR-221miR-222THP-1 cell linemacrophagemonocytecluster of differentiation 4 (CD4)RNAseqhuman immunodeficiency virus type-1 (HIV-1) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robert Lodge Julian C. Gilmore Jérémy A. Ferreira Barbosa Félix Lombard-Vadnais Éric A. Cohen |
spellingShingle |
Robert Lodge Julian C. Gilmore Jérémy A. Ferreira Barbosa Félix Lombard-Vadnais Éric A. Cohen Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells Viruses microRNA miR-221 miR-222 THP-1 cell line macrophage monocyte cluster of differentiation 4 (CD4) RNAseq human immunodeficiency virus type-1 (HIV-1) |
author_facet |
Robert Lodge Julian C. Gilmore Jérémy A. Ferreira Barbosa Félix Lombard-Vadnais Éric A. Cohen |
author_sort |
Robert Lodge |
title |
Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells |
title_short |
Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells |
title_full |
Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells |
title_fullStr |
Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells |
title_full_unstemmed |
Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells |
title_sort |
regulation of cd4 receptor and hiv-1 entry by micrornas-221 and -222 during differentiation of thp-1 cells |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2017-12-01 |
description |
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. |
topic |
microRNA miR-221 miR-222 THP-1 cell line macrophage monocyte cluster of differentiation 4 (CD4) RNAseq human immunodeficiency virus type-1 (HIV-1) |
url |
https://www.mdpi.com/1999-4915/10/1/13 |
work_keys_str_mv |
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