Rev regulates translation of human immunodeficiency virus type 1 RNAs

1 Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK 2 Department of Biological Sciences, University of Warwick, Warwick CV4 7AL, UK 3 Christian Doppler Laboratory for Gene Therapeutic Vectors, Research Institute of Virology and Biomedicine, University for Veterinary Sciences, Vienna, Austria Correspondence Andrew M. L. Lever amll1{at}mole.bio.cam.ac.uk Full-length human immunodeficiency virus type 1 (HIV-1) RNA acts as both mRNA, encoding Gag and Gag–Pol polyproteins, and genomic RNA. Translation of this RNA must be tightly controlled to allow sufficient protein synthesis prior to a switch to particle production. The viral protein Rev stimulates nuclear export of unspliced HIV-1 RNAs containing the Rev response element, but may also stimulate translation of these RNAs. We previously identified an additional Rev binding site in the 5' untranslated region of the HIV-1 RNA. We show that Rev inhibits translation non-specifically at high concentrations and stimulates translation of HIV-1 RNAs at intermediate concentrations in vitro . Stimulation is dependent on the presence of the Rev binding site within the 5' untranslated region and not on the Rev response element. In COS-1 cells, translation from an HIV-1 reporter is specifically increased by coexpression of Rev.