Garrett E D, Cullen B R
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
J Virol. 1992 Jul;66(7):4288-94. doi: 10.1128/JVI.66.7.4288-4294.1992.
The Rev proteins of the related but distinct human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation for this observation is that HIV-2 Rev is unable to interact with the HIV-1 Rev-response element (RRE1). However, an analysis of the biological activity of chimeric proteins derived from HIV-1 and HIV-2 Rev reveals that this target specificity does not map to the Rev RNA binding domain but is instead primarily determined by sequences known to mediate Rev multimerization. Both HIV-1 and HIV-2 Rev are shown to bind the RRE1 in vitro with identical RNA sequence specificity. The observation that HIV-2 Rev can inhibit RRE1-dependent HIV-1 Rev function in trans indicates that the direct interaction of HIV-2 Rev with the RRE1 also occurs in vivo. These data suggest that HIV-2 Rev forms a protein-RNA complex with the RRE1 that leads to only minimal Rev activity. It is hypothesized that this low level of Rev function results from the incomplete and/or aberrant multimerization of HIV-2 Rev on this heterologous RNA target sequence.
相关但不同的人类免疫缺陷病毒1型和2型（HIV-1和HIV-2）的Rev蛋白表现出不完全的功能互作性。对此观察结果的一种可能解释是，HIV-2 Rev无法与HIV-1 Rev反应元件（RRE1）相互作用。然而，对源自HIV-1和HIV-2 Rev的嵌合蛋白的生物学活性分析表明，这种靶标特异性并不定位于Rev RNA结合结构域，而是主要由已知介导Rev多聚化的序列决定。研究表明，HIV-1和HIV-2 Rev在体外均以相同的RNA序列特异性结合RRE1。HIV-2 Rev能够反式抑制依赖RRE1的HIV-1 Rev功能，这一观察结果表明HIV-2 Rev与RRE1的直接相互作用在体内也会发生。这些数据表明，HIV-2 Rev与RRE1形成了一种蛋白质-RNA复合物，导致Rev活性极低。据推测，这种低水平的Rev功能是由HIV-2 Rev在这种异源RNA靶序列上不完全和/或异常的多聚化所致。
