SEQUENCE SPECIFICITY IN THE HIGHER-ORDER INTERACTION OF THE REV PROTEIN OF HIV-1 WITH ITS TARGET SEQUENCE, THE RRE

The Rev protein of human immunodeficiency virus type 1 (HIV-1) multime rizes along RNAs containing the Rev target sequence, the RRE. Although sequence-specific information is recognized in the high affinity or i nitial interaction, it is not known what role RNA-contained informatio n plays in higher-order binding events. We have quantitatively studied the binding of Rev protein to the primary Rev binding domain (II + II I) of wild-type and mutant RREs. RRE mutations that retain the basic s econdary structure of wild type can separately and differentially alte r the Kds for formation of the first, second, and third ReV/RRE comple xes (C1, C2, and C3). The data suggest that Rev recognizes sequence-sp ecific information in the RRE when it forms higher-order complexes. Ho wever, the formation of higher-order complexes is not as dependent on sequence-specific information as the first or lower order binding iter action, which involves recognition of the high-affinity site.