INHIBITION OF HIV TYPE-1 RNA DIMERIZATION BY ANTISENSE DNA CORRESPONDING TO THE 17-NUCLEOTIDE SEQUENCE DOWNSTREAM FROM THE SPLICE DONOR SITE OF HIV TYPE-1 RNA

HIV-1 RNA dimerization involves at least two key regions, one located upstream from the splice donor (SD) site, and the other located downst ream from the SD site, To determine the precise location and the mecha nism of action of the downstream region, we constructed a model system using a synthetic HIV-1 RNA fragment (HXB2, 455-1146), which dimerize d at relatively low salt concentrations (100 mM KCI, 1 mM MgCl2), We t ested in this system antisense DNAs that are complementary to both the upstream and downstream regions of HIV-1 RNA for their possible inhib itory effects on dimerization, Antisense DNAs complementary to nucleot ides 773-789 located downstream from the SD site effectively inhibited dimerization of HIV-1 RNA, These inhibitory antisense DNAs hybridized with the diner form of HIV-1 RNA, and dissociated the diner into mono mers. However, antisense DNAs complementary to the region upstream fro m the SD site did not hybridize with the dimer, although they inhibite d RNA dimerization and also dissociated the preformed dimer.