Malim M H, McCarn D F, Tiley L S, Cullen B R
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
J Virol. 1991 Aug;65(8):4248-54. doi: 10.1128/JVI.65.8.4248-4254.1991.
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.
1型人类免疫缺陷病毒的复制需要病毒编码的Rev蛋白的功能性表达。这种核转录激活因子与其病毒靶序列Rev反应元件的结合，诱导未剪接病毒mRNA的细胞质表达。Rev激活结构域的突变产生具有正常RNA结合能力的无活性蛋白，这些蛋白以反式显性方式抑制野生型Rev功能。在此，我们报告激活结构域至少包含九个氨基酸，其中四个是间隔关键的亮氨酸。在其他灵长类和非灵长类慢病毒Rev蛋白中该必需序列的保留表明，这种富含亮氨酸的基序在进化过程中高度保守。这一结论，连同观察到的多种真核细胞类型对Rev功能的允许性，表明Rev激活结构域的靶标可能是核mRNA转运或剪接所固有的高度保守的细胞蛋白。
