DIMERIZATION OF HIV-1(LAI) RNA AT LOW IONIC-STRENGTH - AN AUTOCOMPLEMENTARY SEQUENCE IN THE 5' LEADER REGION IS EVIDENCED BY AN ANTISENSE OLIGONUCLEOTIDE

Genomic human immunodeficiency virus type 1 (HIV-1) RNA consists of tw o identical RNA molecules joined noncovalently near their 5' ends in a region called the dimer linkage structure (DLS). Previous work has sh own that the putative DLS is localized in a 113-nucleotide domain enco mpassing the 5' end of the gag gene. This region contains conserved pu rine tracks that are thought to mediate dimerization through purine qu artets. However, recently, an HIV-1(Mal) RNA dimerization model was pr oposed as the HIV-1(Mal) RNA dimerization initiation site, involving a nother region upstream from the splice donor site and possibly confine d within a stem-loop. In the present study, we have investigated the d imerization of HIV-1(Lai) RNA, using in vitro dimerization assays unde r conditions of low ionic strength, predictive RNA secondary structure s determined by computer folding, and antisense DNA oligonucleotides i n order to discriminate between these two models. Our results suggest that purine quartets are not involved in the dimer structure of HIV-1( Lai) RNA and have led to the identification of a region upstream from the splice donor site. This region, comprising an autocomplementary se quence in a possible stem-loop structure, is responsible for the forma tion of dimeric HIV-1(Lai) RNA.