TY - JOUR
T1 - Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator
T2 - Essential residues near the amino terminus
AU - Hope, Thomas J.
AU - McDonald, David
AU - Huang, Xiaojian
AU - Low, Jennifer
AU - Parslow, Tristram G.
PY - 1990
Y1 - 1990
N2 - The expression of certain mRNAs from human immunodeficiency virus type 1 (HIV-1) is controlled by the viral transactivator Rev, a nucleolar protein that binds a cis-acting element in these mRNAs. Rev is encoded by two viral exons that specify amino acids 1 to 26 and 27 to 116, respectively. Earlier studies have mapped essential regions of the protein that are encoded in the second exon. By further mutational analysis of Rev, we have now identified a novel locus encoded by the first exon that also is essential for transactivation in vivo. Defined by mutations at residues 14 to 20, this locus coincides with a cluster of positively charged and nonpolar amino acids that is conserved in Rev proteins of all known primate immunodeficiency viruses. Rev proteins that contained mutations at this site were defective in both nuclear localization and transactivation and did not function as trans-dominant inhibitors of wild-type Rev. Fusion of these mutants to a heterologous nuclear protein complemented the defect in localization but did not restore biological activity. Our findings suggest that this N-terminal locus may play a direct role in transactivation, perhaps contributing to essential protein-protein interactions or forming part of the RNA-binding domain of Rev.
AB - The expression of certain mRNAs from human immunodeficiency virus type 1 (HIV-1) is controlled by the viral transactivator Rev, a nucleolar protein that binds a cis-acting element in these mRNAs. Rev is encoded by two viral exons that specify amino acids 1 to 26 and 27 to 116, respectively. Earlier studies have mapped essential regions of the protein that are encoded in the second exon. By further mutational analysis of Rev, we have now identified a novel locus encoded by the first exon that also is essential for transactivation in vivo. Defined by mutations at residues 14 to 20, this locus coincides with a cluster of positively charged and nonpolar amino acids that is conserved in Rev proteins of all known primate immunodeficiency viruses. Rev proteins that contained mutations at this site were defective in both nuclear localization and transactivation and did not function as trans-dominant inhibitors of wild-type Rev. Fusion of these mutants to a heterologous nuclear protein complemented the defect in localization but did not restore biological activity. Our findings suggest that this N-terminal locus may play a direct role in transactivation, perhaps contributing to essential protein-protein interactions or forming part of the RNA-binding domain of Rev.
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U2 - 10.1128/jvi.64.11.5360-5366.1990
DO - 10.1128/jvi.64.11.5360-5366.1990
M3 - Article
C2 - 2120472
AN - SCOPUS:0025149054
VL - 64
SP - 5360
EP - 5366
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 11
ER -