CELLULAR PROTEIN MODULATES EFFECTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV

Replication of human immunodeficiency virus type 1 requires expression of the viral trans activator Rev. Rev binds to a highly structured RN A, the Rev response element, which is present in singly spliced and un spliced genomic viral RNAs. Although Rev helps to transport these tran scripts from the nucleus to the cytoplasm, the mechanism(s) involved i s not fully understood. Using the yeast two-hybrid system, we isolated a murine protein (YL2) that interacts with the basic domain of Rev, w hich is essential for the function of Rev in vivo and for the inhibito ry splicing activity of Rev in vitro. YL2 has 92% identity to a human 32-kDa protein (p32), which copurifies with alternative splicing facto r SF2/ASF. Furthermore, we found that whereas expression of YL2 greatl y potentiated the activity of Rev, antisense YL2 transcripts blocked t he effects of Rev in mammalian cells. YL2 also increased the activitie s of Res on the Res response element and of hybrid Rev proteins fused to Tat and the coat protein of bacteriophage MS2 on their respective R NAs. Thus, YL2 or p32 is a cellular protein that modulates the functio n of human immunodeficiency virus type 1 Rev.