Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.
Human immunodeficiency virus type 1 (HIV-1) encodes a nuclear trans-activator, termed Rev, that is required for the expression of the viral structural proteins and, hence, for viral replication. The Rev protein acts posttranscriptionally to induce the sequence-specific nuclear export of unspliced HIV-1 mRNA species that are otherwise excluded from the cell cytoplasm. We have used site-directed mutagenesis to identify two distinct regions of the HIV-1 Rev protein that are required for in vivo biological activity. The larger and more N-terminal of these two regions includes, but extends beyond, an arginine-rich sequence element required for nuclear localization. Mutation of a second, more C-terminal Rev protein sequence element was found to yield defective Rev proteins that act as trans-dominant inhibitors of Rev function. These Rev mutants are shown to inhibit HIV-1 replication when expressed in transfected cells and may have potential application in the treatment of HIV-1 related disease.
Malim
M H
MH
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Böhnlein
S
S
Hauber
J
J
Cullen
B R
BR
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D006678:HIV / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D011233:Precipitin Tests; D012097:Repressor Proteins / Q000502:physiology; D012191:Retroviridae Proteins / Q000502:physiology*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D012191:Retroviridae Proteins; D014157:Transcription Factors