Specific recognition of the HIV-1 genomic RNA by the Gag precursor

The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse mammary tumor virus (MMTV) genomic RNA

“…Until recently SL3, which is present downstream of mSD, had been proposed to be the main HIV-1 packaging signal since it harbors a conserved region containing a GGAG tetraloop that has been shown to bind NC [43]. However, it has now been shown that SL1, in addition to containing the HIV-1 DIS, also harbors a single-stranded purine rich internal loop (ssPurine: GAGG) that acts as the main site for HIV-1 Gag binding during gRNA packaging [26,30,44,45]. This internal ssPurine loop as well as the DIS, however, are located upstream of the mSD and therefore are part of both the spliced and unspliced viral mRNA.…”

“…This internal ssPurine loop as well as the DIS, however, are located upstream of the mSD and therefore are part of both the spliced and unspliced viral mRNA. Thus, in the case of HIV-1, selection of the gRNA for packaging is likely to be dependent upon the higher order structure of the major packaging determinant of the gRNA which is disrupted upon splicing [26,30,44,45]. In the case of HIV-2, even though both the spliced and unspliced viral mRNAs harbor RNA packaging sequences, only the unspliced message is packaged into nascently formed virus particle since HIV-2 Gag preferentially package gRNA in cis [46–48].…”

“…Several riboswitch models have been proposed for HIV-1 [50–53], and in the case of FIV, the existence of dual structures has been validated by SHAPE and RNA dimerization assays [54]. Flexibility in retroviral gRNA is created via long-range interactions that have now been observed in several retroviruses, from HIV-1, FIV, MLV, to MPMV and MMTV [6,25,26,33,55–59]. The DIS in one conformation is occluded by base pairing and not available for dimerization, thus earmarking this RNA for translation, while the DIS in the other conformation is available as an apical loop on a stem loop, thus allowing dimerization and packaging of the dimeric RNA [54].…”

“…Pal II (5ʹ CUGCAG 3ʹ) has been shown to act as the dimerization initiation site (DIS) for MMTV gRNA from amongst four other palindromes within the 5ʹ UTR of the viral genome [25]. The presence of a stretch of purines in the packaging sequences on retroviral gRNA has been proposed to facilitate RNA packaging by functioning as a potential NC binding site [26–31]. It is also interesting to note that the positioning of the purine-rich loop in MMTV adjacent to the pal II loop is reminiscent of the situation found in Mason-Pfizer monkey virus (MPMV) [32,33].…”

A Short Sequence Motif in the 5′ Leader of the HIV-1 Genome Modulates Extended RNA Dimer Formation and Virus Replication

“…The combined experimental results indicate that the actual sequence of this motif is important, which may suggest the sequence specific binding of a protein co-factor. The most likely candidate is the viral nucleocapsid/Gag protein that is known to occupy multiple sites within the 5Ј leader to support several RNA functions (34,73,74).…”