Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism

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Abstract
The retroviral genome consists of two identical RNA molecules joined close to their 5′ ends by the dimer linkage structure. Recent findings Indicated that retroviral RNA dimerization and encapsidation are probably related events during virion assembly. We studied the cation-induced dimerization of HIV-1 RNA and results indicate that all in vitro generated HIV-1 RNAs containing a 100 nucleotide domain downstream from the 5′ splice site are able to dimerize. RNA dimerization depends on the concentration of RNA, mono- and multlvalent cations, the size of the monovalent cation, temperature, and pH. Up to 75% of HIV-1 RNA Is dimeric in the presence of spermidlne. HIV-1 RNA dimer Is fairly resistant to denaturing agents and unaffected by Intercalating drugs. Antlsense HIV-1 RNA does not dimerize but heterodlmers can be formed between HIV-1 RNA and either MoMuLV or RSV RNA. Therefore retroviral RNA dimerization probably does not simply proceed through mechanisms involving Watson-Crick base-pairing. Neither adenine and cytoslne protonatlon, nor quartets containing only guanines appear to determine the stability of the HIV-1 RNA dimer, while quartets involving both adenlne(s) and guanine(s) could account for our results. A consensus sequence PuGGAPuA found in the putative dimerization-encapsldation region of all retroviral genomes examinated may participate in the dimerization process.