5' leader region of lentiviral genomic RNA and proposed structural conformations. The landmark sequences with known functions of HIV-2 (A), SIV (B), and HIV-1 (C) leader RNAs are indicated by boxes with the names indicated above. TAR, polyA signal, PBS, Ψ, SL1, SD, and gag represent the trans-activation region, the polyA signal domain, the primer-binding site, the major encapsidation signal, the stem-loop 1, the major splice donor site, and the 5' end of the Gag protein coding region, respectively. The numbering corresponds to the genomic RNA position. HIV-2 and SIV Ψ sequences correspond to nts 380–408, and 381–409, respectively ([8, 53]). HIV-1 Ψ is represented by the stem-loop 3 structure (nts 312–325, ). D. Schematics of the proposed conformations of leader RNAs that impair SL1-mediated dimerization are shown. HIV-1 leader RNA can form an extensive, long-range base pairing interaction between the polyA signal and SL1 domains (called LDI) . HIV-2 leader RNA can make a long-range base pairing interaction (called CGI for C-box – G-box interaction) between a sequence located between the polyA and PBS domains and another one located at the gag translation initiation region (C-box and G-box, respectively). Formation of CGI impairs SL1-mediated dimerization in HIV-2 ([21, 25]). E. The proposed conformation of HIV-1 leader RNA that favors dimerization is characterized by a distinct branched multiple-hairpin structure (BMH) that contains an intact CGI . F. Representation of HIV-2/SIV (top) and HIV-1 (bottom) CGI base pairing models ([17, 25]). Numbers and nucleotides in parentheses represent the SIV equivalent of HIV-2 numbers and nucleotides. The translation initiation codon of the gag gene is underlined.