Mutational definition of the human immunodeficiency virus type 1 Rev activation domain.
Replication of human immunodeficiency virus type 1 requires the functional expression of the virally encoded Rev protein. The binding of this nuclear trans activator to its viral target sequence, the Rev-response element, induces the cytoplasmic expression of unspliced viral mRNAs. Mutation of the activation domain of Rev generates inactive proteins with normal RNA binding capabilities that inhibit wild-type Rev function in a trans-dominant manner. Here, we report that the activation domain comprises a minimum of nine amino acids, four of which are critically spaced leucines. The preservation of this essential sequence in other primate and nonprimate lentivirus Rev proteins indicates that this leucine-rich motif has been highly conserved during evolution. This conclusion, taken together with the observed permissiveness of a variety of eukaryotic cell types for Rev function, suggests that the target for the activation domain of Rev is likely to be a highly conserved cellular protein(s) intrinsic to nuclear mRNA transport or splicing.
Malim
M H
MH
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
McCarn
D F
DF
Tiley
L S
LS
Cullen
B R
BR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D011233:Precipitin Tests; D011323:Primates; D011533:Proviruses / Q000235:genetics*; D011784:Quail; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D015696:Gene Products, tat; D012333:RNA, Messenger; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus