NUCLEOCYTOPLASMIC TRANSPORT OF THE REV PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IS DEPENDENT ON THE ACTIVATION DOMAIN OF THE PROTEIN

The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev , which is required for the cytoplasmic expression of unspliced and in completely spliced viral mRNAs, is located predominantly in the nucleo lus. In this study, we show that Rev translocates from the nucleolus t o the cytoplasm in HeLa and COS cells transfected with Rev under condi tions where rRNA synthesis is inhibited (e.g., with actinomycin D). Do minant-negative mutants with mutations in the activation domain of Rev , which are known to inhibit wildtype Rev function in trans, are unabl e to leave the nucleus upon actinomycin D treatment. More importantly, when present in excess, these mutants inhibit the translocation of wi ld-type Rev. This correlation of inhibitory activities suggests that R ev function depends on its transport to and presence (at least transie nt) in the cytoplasm. In this context, we discuss the possibility that Rev is actively involved in the transport of HIV-1-specific mRNAs con taining the Rev response element (a highly structured RNA sequence, wh ich is specifically recognized by the Rev trans-activator). We also di scuss the potential of nucleocytoplasmic export of Rev as a target for anti-HIV chemotherapy. (C) 1995 Academic Press, Inc.