Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes.
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 cells. 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.
Huang
Jialing
J
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Wang
Fengxiang
F
Argyris
Elias
E
Chen
Keyang
K
Liang
Zhihui
Z
Tian
Heng
H
Huang
Wenlin
W
Squires
Kathleen
K
Verlinghieri
Gwen
G
Zhang
Hui
H
D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010957:Plasmids; D014162:Transfection; D017735:Virus Latency / Q000187:drug effects*
D035683:MicroRNAs