Cellular microRNAexpression correlates with susceptibility of monocytes/macrophages to HIV-1 infection

Although both monocytes and macro- phages possess essential requirements for HIV-1 entry, peripheral blood mono- cytes are infrequently infected with HIV-1 in vivo and in vitro. In contrast, tissue macrophages and monocyte-derived mac- rophages in vitro are highly susceptible to infection with HIV-1 R5 tropic strains. We investigated intracellular anti-HIV-1 factors that contribute to differential sus- ceptibility of monocytes/macrophages to HIV-1 infection. Freshly isolated mono- cytes from peripheral blood had signifi- cantly higher levels of the anti-HIV-1 mi- croRNAs (miRNA, miRNA-28, miRNA-150, miRNA-223, and miRNA-382) than monocyte-derived macrophages. The suppression of these anti-HIV-1 miRNAs in monocytes facilitates HIV-1 infectivity, whereas increase of the anti-HIV-1 miRNA expression in macrophages inhibited HIV-1 replication. These findings provide compelling and direct evidence at the molecular level to support the notion that intracellular anti-HIV-1 miRNA-mediated innate immunity may have a key role in protecting monocytes/macrophages from HIV-1 infection. (Blood. 2009;113:671-674)