Abstract
The genome of the retroviruses is a dimer composed by two homologous copies of genomic RNA (gRNA) molecules of positive polarity. The dimerization process allows two gRNA molecules to be non-covalently linked together through intermolecular base-pairing. This step is critical for the viral life cycle and is highly conserved among retroviruses with the exception of spumaretroviruses. Furthermore, packaging of two gRNA copies into viral particles presents an important evolutionary advantage for immune system evasion and drug resistance. Recent studies reported RNA switches models regulating not only gRNA dimerization, but also translation and packaging, and a spatio-temporal characterization of viral gRNA dimerization within cells are now at hand. This review summarizes our current understanding on the structural features of the dimerization signals for a variety of retroviruses (HIVs, MLV, RSV, BLV, MMTV, MPMV…), the mechanisms of RNA dimer formation and functional implications in the retroviral cycle.
Highlights
During the late phase of their replication cycle, retroviruses package two homologous copies of their genomic RNA in order to produce infectious viral particles
For several retroviruses, e.g., human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MuLV), genomic RNA (gRNA) dimerization is critical for selective packaging of the genome (Berkhout and van Wamel, 1996; Mougel et al, 1996; Paillart et al, 1996a; McBride and Panganiban, 1997; Mougel and Barklis, 1997; Aagaard et al, 2004; Houzet et al, 2007)
Selective 2 -hydroxyl acylation analyzed by primer extension (SHAPE) and in vitro dimerization assays of mammary tumor virus (MMTV) gRNA fragments revealed that loose dimer formation is potentially mediated by two palindromic sequences, respectively, within the primer binding site (PBS-Pal) and in a bifurcated stem-loop structure (SL4) located between the PBS and the translation initiation codon of gag (Pal II) (Figure 3A)
Summary
During the late phase of their replication cycle, retroviruses package two homologous copies of their genomic RNA (gRNA) in order to produce infectious viral particles. Selective 2 -hydroxyl acylation analyzed by primer extension (SHAPE) and in vitro dimerization assays of MMTV gRNA fragments revealed that loose dimer formation is potentially mediated by two palindromic sequences, respectively, within the primer binding site (PBS-Pal) and in a bifurcated stem-loop structure (SL4) located between the PBS and the translation initiation codon of gag (Pal II) (Figure 3A).
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