The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222.
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.
Deptartment of Biomedicine and Prevention; University of Rome "Tor Vergata"; Rome, Italy.
Elisa
E
Orecchini
Laboratory of Immunoinfectivology; Bambino Gesù Children's Hospital; IRCCS, Rome, Italy.
Margherita
M
Doria
Deptartment of Biomedicine and Prevention; University of Rome "Tor Vergata"; Rome, Italy.
Alessandro
A
Michienzi
Laboratory of Immunoinfectivology; Bambino Gesù Children's Hospital; IRCCS, Rome, Italy.
Erica
E
Giuliani
Laboratory of Immunoinfectivology; Bambino Gesù Children's Hospital; IRCCS, Rome, Italy.
Lia
L
Vassena
Deptartment of Biomedicine and Prevention; University of Rome "Tor Vergata"; Rome, Italy.
Silvia Anna
SA
Ciafrè
Deptartment of Biomedicine and Prevention; University of Rome "Tor Vergata"; Rome, Italy.
Maria Giulia
MG
Farace
Deptartment of Biomedicine and Prevention; University of Rome "Tor Vergata"; Rome, Italy.
Silvia
S
Galardi
D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D015704:CD4 Antigens; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D054322:tat Gene Products, Human Immunodeficiency Virus; C525710:MIR222, human
CD4; HIV-1; NFkB; microRNAs; post-transcriptional regulation