Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor
Macrophages are heterogeneous immune cells with distinct origins, phenotypes, functions, and tissue localization. Their susceptibility to HIV-1 is subject to variations from permissiveness to resistance, owing in part to regulatory microRNAs. Here, we used RNA sequencing (RNA-seq) to examine the exp...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717313050 |
| _version_ | 1819031292060106752 |
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| author | Robert Lodge Jérémy A. Ferreira Barbosa Félix Lombard-Vadnais Julian C. Gilmore Alexandre Deshiere Annie Gosselin Tomas Raul Wiche Salinas Mariana G. Bego Christopher Power Jean-Pierre Routy Petronela Ancuta Michel J. Tremblay Éric A. Cohen |
| author_facet | Robert Lodge Jérémy A. Ferreira Barbosa Félix Lombard-Vadnais Julian C. Gilmore Alexandre Deshiere Annie Gosselin Tomas Raul Wiche Salinas Mariana G. Bego Christopher Power Jean-Pierre Routy Petronela Ancuta Michel J. Tremblay Éric A. Cohen |
| author_sort | Robert Lodge |
| collection | DOAJ |
| description | Macrophages are heterogeneous immune cells with distinct origins, phenotypes, functions, and tissue localization. Their susceptibility to HIV-1 is subject to variations from permissiveness to resistance, owing in part to regulatory microRNAs. Here, we used RNA sequencing (RNA-seq) to examine the expression of >400 microRNAs in productively infected and bystander cells of HIV-1-exposed macrophage cultures. Two microRNAs upregulated in bystander macrophages, miR-221 and miR-222, were identified as negative regulators of CD4 expression and CD4-mediated HIV-1 entry. Both microRNAs were enhanced by tumor necrosis factor alpha (TNF-α), an inhibitor of CD4 expression. MiR-221/miR-222 inhibitors recovered HIV-1 entry in TNF-α-treated macrophages by enhancing CD4 expression and increased HIV-1 replication and spread in macrophages by countering TNF-α-enhanced miR-221/miR-222 expression in bystander cells. In line with these findings, HIV-1-resistant intestinal myeloid cells express higher levels of miR-221 than peripheral blood monocytes. Thus, miR-221/miR-222 act as effectors of the antiviral host response activated during macrophage infection that restrict HIV-1 entry. |
| first_indexed | 2024-12-21T06:43:43Z |
| format | Article |
| id | doaj.art-b79fa5ac2bb9497c9de47770d7042beb |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T06:43:43Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b79fa5ac2bb9497c9de47770d7042beb2022-12-21T19:12:38ZengElsevierCell Reports2211-12472017-10-0121114115310.1016/j.celrep.2017.09.030Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral ReceptorRobert Lodge0Jérémy A. Ferreira Barbosa1Félix Lombard-Vadnais2Julian C. Gilmore3Alexandre Deshiere4Annie Gosselin5Tomas Raul Wiche Salinas6Mariana G. Bego7Christopher Power8Jean-Pierre Routy9Petronela Ancuta10Michel J. Tremblay11Éric A. Cohen12Institut 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, CanadaAxe des Maladies Infectieuses et Immunitaires, CR-CHU de Québec-Université Laval, Pavillon CHUL, Quebec City, QC, G1V 4G2, CanadaCR-CHUM, Montreal, QC, H2X 0A9, CanadaCR-CHUM, Montreal, QC, H2X 0A9, CanadaInstitut de Recherches Cliniques de Montréal, Montreal, QC, H2W 1R7, CanadaDivision of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, T6G 2S2, CanadaChronic Viral Illness Service and Division of Hematology, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, CanadaCR-CHUM, Montreal, QC, H2X 0A9, CanadaAxe des Maladies Infectieuses et Immunitaires, CR-CHU de Québec-Université Laval, Pavillon CHUL, Quebec City, QC, G1V 4G2, CanadaInstitut de Recherches Cliniques de Montréal, Montreal, QC, H2W 1R7, CanadaMacrophages are heterogeneous immune cells with distinct origins, phenotypes, functions, and tissue localization. Their susceptibility to HIV-1 is subject to variations from permissiveness to resistance, owing in part to regulatory microRNAs. Here, we used RNA sequencing (RNA-seq) to examine the expression of >400 microRNAs in productively infected and bystander cells of HIV-1-exposed macrophage cultures. Two microRNAs upregulated in bystander macrophages, miR-221 and miR-222, were identified as negative regulators of CD4 expression and CD4-mediated HIV-1 entry. Both microRNAs were enhanced by tumor necrosis factor alpha (TNF-α), an inhibitor of CD4 expression. MiR-221/miR-222 inhibitors recovered HIV-1 entry in TNF-α-treated macrophages by enhancing CD4 expression and increased HIV-1 replication and spread in macrophages by countering TNF-α-enhanced miR-221/miR-222 expression in bystander cells. In line with these findings, HIV-1-resistant intestinal myeloid cells express higher levels of miR-221 than peripheral blood monocytes. Thus, miR-221/miR-222 act as effectors of the antiviral host response activated during macrophage infection that restrict HIV-1 entry.http://www.sciencedirect.com/science/article/pii/S2211124717313050HIV-1macrophagemicroRNATNF-αmacrophage activationCD4miR-221miR-222antiviralRNA-seq |
| spellingShingle | Robert Lodge Jérémy A. Ferreira Barbosa Félix Lombard-Vadnais Julian C. Gilmore Alexandre Deshiere Annie Gosselin Tomas Raul Wiche Salinas Mariana G. Bego Christopher Power Jean-Pierre Routy Petronela Ancuta Michel J. Tremblay Éric A. Cohen Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor Cell Reports HIV-1 macrophage microRNA TNF-α macrophage activation CD4 miR-221 miR-222 antiviral RNA-seq |
| title | Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor |
| title_full | Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor |
| title_fullStr | Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor |
| title_full_unstemmed | Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor |
| title_short | Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor |
| title_sort | host micrornas 221 and 222 inhibit hiv 1 entry in macrophages by targeting the cd4 viral receptor |
| topic | HIV-1 macrophage microRNA TNF-α macrophage activation CD4 miR-221 miR-222 antiviral RNA-seq |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717313050 |
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