IN-VITRO SELECTION OF RNAS THAT BIND TO THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG POLYPROTEIN

RNA ligands that bind to the human immunodeficiency virus type-1 (HIV- 1) gag polyprotein with 10(-9) M affinity were isolated from a complex pool of RNAs using an in vitro selection method, The ligands bind to two different regions within gag, either to the matrix protein or to t he nucleocapsid protein, Binding of a matrix ligand to gag did not int erfere with the binding of a nucleocapsid ligand, and binding of a nuc leocapsid ligand to gag did not interfere with the binding of a matrix ligand. However, binding of a nucleocapsid ligand to gag did interfer e with binding of an RNA containing the HIV-1 RNA packaging element (p si), even though the sequence of the nucleocapsid ligand is not simila r to psi. The minimal sequences required for the ligands to bind to ma trix or nucleocapsid were determined, Minimal nucleocapsid ligands are predicted to form a stem-loop structure that has a self-complementary sequence at one end, Minimal matrix ligands are predicted to form a d ifferent stem-loop structure that has a CAARU loop sequence, The prope rties of these RNA ligands may provide tools for studying RNA interact ions with matrix and nucleocapsid, and a novel method for inhibiting H IV replication.