Letter abstract
Nature Medicine 13, 1241 - 1247 (2007)
Published online: 30 September 2007 | doi:10.1038/nm1639
Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes
Jialing Huang1, Fengxiang Wang1, Elias Argyris1, Keyang Chen1, Zhihui Liang1,2, Heng Tian1, Wenlin Huang2, Kathleen Squires1, Gwen Verlinghieri1 & Hui Zhang1
The latency of human immunodeficiency virus type 1 (HIV-1) in resting primary CD4+ T cells is the major barrier for the eradication of the virus in patients on suppressive highly active antiretroviral therapy (HAART). Even with optimal HAART treatment, replication-competent HIV-1 still exists in resting primary CD4+ T cells1, 2, 3, 4. Multiple restriction factors that act upon various steps of the viral life cycle could contribute to viral latency. Here we show that cellular microRNAs (miRNAs) potently inhibit HIV-1 production in resting primary CD4+ T cells. We have found that the 3' ends of HIV-1 messenger RNAs are targeted by a cluster of cellular miRNAs including miR-28, miR-125b, miR-150, miR-223 and miR-382, which are enriched in resting CD4+ T cells as compared to activated CD4+ T cells. Specific inhibitors of these miRNAs substantially counteracted their effects on the target mRNAs, measured either as HIV-1 protein translation in resting CD4+ T cells transfected with HIV-1 infectious clones, or as HIV-1 virus production from resting CD4+ T cells isolated from HIV-1–infected individuals on suppressive HAART. Our data indicate that cellular miRNAs are pivotal in HIV-1 latency and suggest that manipulation of cellular miRNAs could be a novel approach for purging the HIV-1 reservoir.
- Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
- Cancer Center, Sun Yatsen University, Guangzhou, Guangdong, 510060, China.
Correspondence to: Hui Zhang1 e-mail: hui.zhang@jefferson.edu
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