Interaction of the second coding exon of Tat with human EF-1 delta delineates a mechanism for HIV-1-mediated shut-off of host mRNA translation

Biochem Biophys Res Commun. 1998 Mar 17;244(2):384-9. doi: 10.1006/bbrc.1998.8274.


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-cell activator, and an inducer of cellular apoptosis, amongst others. For 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 second exon of Tat has remained largely unknown, its integrity in lentiviral genomes suggests biological importance, possibly a role in non-transcriptional activities. To understand better the biology of the second exon of Tat in HIV-1 infection of cells, we have searched for cellular proteins that bind specifically to this protein domain. Here, we report that the human translation elongation factor 1-delta (EF-1 delta) binds to the second exon of HIV-1 Tat. Interaction between Tat and EF-1 delta dramatically reduces the efficiency of the translation of cellular, but not viral, mRNAs. These findings suggest that a non-transcriptional activity of Tat modulates cellular protein synthesis, thereby affecting the metabolism of host cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • Exons
  • Genes, tat*
  • HIV-1 / genetics*
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • In Vitro Techniques
  • Molecular Sequence Data
  • Peptide Elongation Factor 1
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / metabolism*
  • Protein Binding
  • Protein Biosynthesis*
  • RNA, Messenger / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Ubiquitin-Protein Ligases


  • Immediate-Early Proteins
  • Peptide Elongation Factor 1
  • Peptide Elongation Factors
  • RNA, Messenger
  • Ubiquitin-Protein Ligases
  • Vmw110 protein, Human herpesvirus 1