Host MicroRNAs-221 and -222 Inhibit HIV-1 Entry in Macrophages by Targeting the CD4 Viral Receptor

Cell Reports

Michel J. Tremblay¹  Alexandre Deshiere¹  Petronela Ancuta²  Tomas Raul Wiche Salinas²  Annie Gosselin²  Jean-Pierre Routy³  Christopher Power⁴  Julian C. Gilmore⁵  Robert Lodge⁵  Jérémy A. Ferreira Barbosa⁵  Éric A. Cohen⁵  Mariana G. Bego⁵  Félix Lombard-Vadnais⁵ 

[1] Axe des Maladies Infectieuses et Immunitaires, CR-CHU de Québec-Université Laval, Pavillon CHUL, Quebec City, QC, G1V 4G2, Canada;CR-CHUM, Montreal, QC, H2X 0A9, Canada;Chronic Viral Illness Service and Division of Hematology, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada;Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, T6G 2S2, Canada;Institut de Recherches Cliniques de Montréal, Montreal, QC, H2W 1R7, Canada;

关键词: HIV-1;    macrophage;    microRNA;    TNF-α;    macrophage activation;    CD4;    miR-221;    miR-222;    antiviral;    RNA-seq;   

DOI  :  10.1016/j.celrep.2017.09.030

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown