EFFECTS OF TRANSLATION INITIATION-FACTOR EIF-5A ON THE FUNCTIONING OFHUMAN T-CELL LEUKEMIA-VIRUS TYPE-I REX AND HUMAN-IMMUNODEFICIENCY-VIRUS REV INHIBITED TRANS DOMINANTLY BY A REX MUTANT DEFICIENT IN RNA-BINDING

The viral transactivator proteins Rex and Rev are necessary for the ex pression of structural proteins of human T-cell leukemia virus type I and human immunodeficiency virus type 1, respectively. Although the in teraction of Rex/Rev with a cellular cofactor(s) has been thought to b e required for Rex/Rev action, there is no suitable system to search f or the cofactor(s) in mammalian cells. We found that a Rex mutant, TAg Rex, which contains a simian virus 40 nuclear localization signal in p lace of the N-terminal 19 amino acids of Rex, could dominantly inhibit wild-type Rex/Rev functions. The inhibition did not require either Re v response element/Rex response element binding or the oligomerization ability of the mutant, but it did require a region around amino acid 90 of the Rex protein, suggesting that TAgRex sequestered the cellular cofactor. Complementation with the eukaryotic translation initiation factor 5A (eIF-5A) in this system could restore the impaired Rex funct ion. These results indicate that eIF-5A is the cofactor indispensable for Rex function. Additionally, by using a two-hybrid system, the homo -oligomer formation of Rex was found to be mediated by the region arou nd amino acid 90 in addition to Tyr-64 and Trp-65 of Rex protein. Thus , eIF-SA may play a part in the formation of the Rex homo oligomer.