INTERACTION OF THE 2ND CODING EXON OF TAT WITH HUMAN EF-1-DELTA DELINEATES A MECHANISM FOR HIV-1-MEDIATED SHUTOFF OF HOST MESSENGER-RNA TRANSLATION

HIV-1 Tat has pleiotropic functions. While its most studied role is to activate transcription from the retroviral long terminal repeat (LTR) -promoter, Tat also has functions as a secretable growth factor, a T-c ell activator, and an inducer of cellular apoptosis, amongst others. F or its transcriptional function, the first coding exon of Tat appears wholly sufficient; however, lentiviruses (HIVs and SIVs) maintain and conserve a second coding exon for Tat. While the function(s) of the se cond exon of Tat has remained largely unknown, its integrity in lentiv iral genomes suggests biological importance, possibly a role in non-tr anscriptional activities. To understand better the biology of the seco nd exon of Tat in HIV-1 infection of cells, we have searched for cellu lar proteins that bind specifically to this protein domain. Here, we r eport that the human translation elongation factor 1-delta (EF-1 delta ) binds to the second exon of HIV-1 Tat. Interaction between Tat and E F-1 delta dramatically reduces the efficiency of the translation of ce llular, but not viral, mRNAs. These findings suggest that a non-transc riptional activity of Tat modulates cellular protein synthesis, thereb y affecting the metabolism of host cells. (C) 1998 Academic Press.