Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation.
Expression of human immunodeficiency virus type 1 (HIV-1) structural proteins requires the presence of the viral trans-activator protein Rev. Rev is localized in the nucleus and binds specifically to the Rev response element (RRE) sequence in viral RNA. Furthermore, the interaction of the Rev activation domain with a cellular cofactor is essential for Rev function in vivo. Using cross-linking experiments and Biospecific Interaction Analysis (BIA) we identify eukaryotic initiation factor 5A (eIF-5A) as a cellular factor binding specifically to the HIV-1 Rev activation domain. Indirect immunofluorescence studies demonstrate that a significant fraction of eIF-5A localizes to the nucleus. We also provide evidence that Rev transactivation is functionally mediated by eIF-5A in Xenopus oocytes. Furthermore, we are able to block Rev function in mammalian cells by antisense inhibition of eIF-5A gene expression. Thus, regulation of HIV-1 gene expression by Rev involves the targeting of RRE-containing RNA to components of the cellular translation initiation complex.
Ruhl
M
M
SANDOZ Research Institute, Vienna, Austria.
Himmelspach
M
M
Bahr
G M
GM
Hammerschmid
F
F
Jaksche
H
H
Wolff
B
B
Aschauer
H
H
Farrington
G K
GK
Probst
H
H
Bevec
D
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D015757:Genes, rev; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D015533:Transcriptional Activation; D000097574:Eukaryotic Translation Initiation Factor 5A
D017931:DNA Primers; D009687:Nuclear Proteins; D010448:Peptide Initiation Factors; D010455:Peptides; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A