Dimerization of retroviral genomic RNAs: structural and functional implications

Abstract

Retroviruses are a family of widespread small animal viruses at the origin of a diversity of diseases. They share common structural and functional properties such as reverse transcription of their RNA genome and integration of the proviral DNA into the host genome, and have the particularity of packaging a diploid genome. The genome of all retroviruses is composed of two homologous RNA molecules that are non-covalently linked near their 5' end in a region called the dimer linkage structure (DLS). There is now considerable evidence that a specific site (or sites) in the 5' leader region of all retroviruses, located either upstream or/and downstream of the major splice donor site, is involved in the dimer linkage. For MoMuLV and especially HIV-1, it was shown that dimerization is initiated at a stem-loop structure named the dimerization initiation site (DIS). The DIS of HIV-1 and related regions in other retroviruses corresponds to a highly conserved structure with a self-complementary loop sequence, that is involved in a typical loop-loop 'kissing' complex which can be further stabilized by long distance interactions or by conformational rearrangements. RNA interactions involved in the viral RNA dimer were postulated to regulate several key steps in retroviral cycle, such as: i) translation and encapsidation: the arrest of gag translation imposed by the highly structured DLS-encapsidation signal would leave the RNA genome available for the encapsidation machinery; and ii) recombination during reverse transcription: the presence of two RNA molecules in particles would be necessary for variability and viability of virus progeny and the ordered structure imposed by the DLS would be required for efficient reverse transcription.