Genomic human immunodeficiency virus type 1 (HIV-1) RNA consists of two identical RNA molecules joined noncovalently near their 5` ends in a region called the dimer linkage structure (DLS). Previous work has shown that the putative DLS is localized in a 113-nucleotide domain encompassing the 5` end of the gag gene. This region contains conserved purine tracks that are thought to mediate dimerization through purine quartets. However, recently, an HIV-1 RNA dimerization model was proposed as the HIV-1 RNA dimerization initiation site, involving another region upstream from the splice donor site and possibly confined within a stem-loop. In the present study, we have investigated the dimerization of HIV-1 RNA, using in vitro dimerization assays under conditions of low ionic strength, predictive RNA secondary structures determined by computer folding, and antisense DNA oligonucleotides in order to discriminate between these two models. Our results suggest that purine quartets are not involved in the dimer structure of HIV-1 RNA and have led to the identification of a region upstream from the splice donor site. This region, comprising an autocomplementary sequence in a possible stem-loop structure, is responsible for the formation of dimeric HIV-1 RNA.

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