The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222

• Published in: RNA biology 2014, Vol.11 (4), p.334-338
• Main Authors: Orecchini, Elisa, Doria, Margherita, Michienzi, Alessandro, Giuliani, Erica, Vassena, Lia, Ciafrè, Silvia Anna, Farace, Maria Giulia, Galardi, Silvia
• Format: Article
• Language: English
• Subjects: Brief Communication; CD4 Antigens - genetics; CD4 Antigens - metabolism; Cell Line; Gene Expression Regulation; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - metabolism; HIV-1 - physiology; Humans; MicroRNAs - genetics; NF-kappa B - metabolism; RNA, Messenger - genetics; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; tat Gene Products, Human Immunodeficiency Virus - metabolism
• ISSN: 1547-6286; 1555-8584
• DOI: 10.4161/rna.28372

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells.