title: miRNA profiles of monocyte-lineage cells are consistent with complicated roles in HIV-1 restriction.
abstract: Long-lived HIV-1 reservoirs include tissue macrophages. Monocyte-derived macrophages are more susceptible to infection and more permissive to HIV-1 replication than monocytes for reasons that may include the effects of different populations of miRNAs in these two cell classes. Specifically, miRs-28-3p, -150, -223, -198, and -382 exert direct or indirect negative effects on HIV-1 and are reportedly downmodulated during monocyte-to-macrophage differentiation. Here, new experimental results are presented along with reviews and analysis of published studies and publicly available datasets, supporting a broader role of miRNAs in HIV-1 restriction than would be suggested by a simple and uniform downregulation of anti-HIV miRNAs during monocyte-to-macrophage differentiation. Although miR-223 is downregulated in macrophages, other putatively antiviral miRNAs are more abundant in macrophages than in monocytes or are rare and/or variably present in both cell classes. Our analyses point to the need for further studies to determine miRNA profiles of monocytes and macrophages, including classic and newly identified subpopulations; examine the sensitivity of miRNA profiling to cell isolation and differentiation protocols; and characterize rigorously the antiviral effects of previously reported and novel predicted miRNA-HIV-1 interactions in cell-specific contexts.
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. jsisk2@jhmi.edu
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Sisk
authors.forename: Janice E
authors.initials: JE
authors.lastname: Clements
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D030541:Databases, Genetic; D004198:Disease Susceptibility / Q000821:virology; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; C525067:MIR223, human; C532045:MIRN29a microRNA, human