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. It is known that every spliced or unspliced HIV-1 mRNA, with the exception of Nef-encoding mRNA, contains the 1.2-kb fragment we used (or a portion of it) in its 3'UTR25 . Thus, these cellular miRNAs, which bind the 1.2-kb fragment of the HIV-1 RNA 3'end, can inhibit the translation of almost all HIV-1-encoded proteins-including Tat and Rev, which are key in the transcription and translocation of viral RNA.