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Blood, 15 January 2009, Vol. 113, No. 3, pp. 671-674.
Prepublished online as a Blood First Edition Paper on November 17, 2008; DOI 10.1182/blood-2008-09-175000.
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Submitted September 5, 2008
Accepted November 2, 2008
Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection
Xu Wang, Li Ye, Wei Hou, Yu Zhou, Yan-Jian Wang, David S. Metzger, and Wen-Zhe Ho*
Division of Allergy and Immunology, Joseph Stokes, Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, United States
Department of Psychiatry, The Center for Studies of Addiction, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
* Corresponding author; email: ho{at}email.chop.edu.
Although both monocytes and macrophages possess essential requirements for HIV-1 entry, peripheral blood monocytes are infrequently infected with HIV-1 in vivo and in vitro. In contrast, tissue macrophages and monocyte-derived macrophages in vitro are highly susceptible to infection with HIV-1 R5 tropic strains. We investigated intracellular anti-HIV-1 factors that contribute to differential susceptibility of monocytes/macrophages to HIV-1 infection. Freshly isolated monocytes from peripheral blood had significantly higher levels of the anti-HIV-1 microRNAs (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, while 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.
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