EUKARYOTIC INITIATION FACTOR-5A IS A CELLULAR TARGET OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV ACTIVATION DOMAIN MEDIATING TRANSACTIVATION

Expression of human immunodeficiency virus type 1 (HIV-1) structural p roteins requires the presence of the viral trans-activator protein Rev . Rev is localized in the nucleus and binds specifically to the Rev re sponse element (RRE) sequence in viral RNA. Furthermore, the interacti on of the Rev activation domain with a cellular cofactor is essential for Rev function in vivo. Using cross-linking experiments and Biospeci fic Interaction Analysis (BIA) we identify eukaryotic initiation facto r 5A (eIF-5A) as a cellular factor binding specifically to the HIV-1 R ev activation domain. Indirect immunofluorescence studies demonstrate that a significant fraction of eIF-5A localizes to the nucleus. We als o provide evidence that Rev trans-activation is functionally mediated by eIF-5A in Xenopus oocytes. Furthermore, we are able to block Rev fu nction in mammalian cells by antisense inhibition of eIF-5A gene expre ssion. Thus, regulation of HIV-1 gene expression by Rev involves the t argeting of RRE-containing RNA to components of the cellular translati on initiation complex.