Limits...
The Life-Cycle of the HIV-1 Gag – RNA Complex

View Article: PubMed Central - PubMed

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) replication is a highly regulated process requiring the recruitment of viral and cellular components to the plasma membrane for assembly into infectious particles. This review highlights the recent process of understanding the selection of the genomic RNA (gRNA) by the viral Pr55Gag precursor polyprotein, and the processes leading to its incorporation into viral particles.

No MeSH data available.


RNA structural models proposed to regulate the packaging and translation of the gRNA. (A) Gag binding is subjected to a mechanism of double regulation. The region upstream of SL1 (present in all viral RNAs) negatively regulates Gag binding. A region upstream of SL1 prevents binding of Gag to SL1 and this negative effect is counteracted by a motif downstream of SL4, present only in gRNA species; (B) The Long Distance Interaction (LDI) proposed to promote translation and the Branched Multiple Hairpin (BMH) proposed to promote packaging; (C) The U5 region is involved in alternative interactions with the dimerization initiation site (DIS) (promoting translation) and the region surrounding the AUG start codon (promoting packaging). A three-way junction, which further extends the U5-AUG interaction and eliminates SL2, is proposed to favour packaging. TAR: Tat responsive element; Poly-A: polyadenylation signal, U5: unique 5′ region, PBS: primer binding site; SL: stem loop; DIS: dimerization initiation site; SD: splice donor; Psi: packaging signal; AUG; start codon.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5035962&req=5

viruses-08-00248-f003: RNA structural models proposed to regulate the packaging and translation of the gRNA. (A) Gag binding is subjected to a mechanism of double regulation. The region upstream of SL1 (present in all viral RNAs) negatively regulates Gag binding. A region upstream of SL1 prevents binding of Gag to SL1 and this negative effect is counteracted by a motif downstream of SL4, present only in gRNA species; (B) The Long Distance Interaction (LDI) proposed to promote translation and the Branched Multiple Hairpin (BMH) proposed to promote packaging; (C) The U5 region is involved in alternative interactions with the dimerization initiation site (DIS) (promoting translation) and the region surrounding the AUG start codon (promoting packaging). A three-way junction, which further extends the U5-AUG interaction and eliminates SL2, is proposed to favour packaging. TAR: Tat responsive element; Poly-A: polyadenylation signal, U5: unique 5′ region, PBS: primer binding site; SL: stem loop; DIS: dimerization initiation site; SD: splice donor; Psi: packaging signal; AUG; start codon.

Mentions: HIV-1 packaging of the gRNA dimer is strongly favored over abundant cellular RNAs and viral spliced mRNA species. As previously described, the specific recognition motif for the Gag precursor was identified as the internal loop and distal helix of SL1 [13,68]. These results were unexpected as SL1 is located 5′ of the spliced donor site and is thus present both on the genomic and on the spliced viral RNAs, suggesting a mechanism preventing Gag binding to SL1 in spliced viral RNA. Consistent with this idea, SL1 promotes exclusively the packaging of the unspliced gRNA, whereas spliced viral RNAs deleted for SL1 are incorporated with equal efficiency as spliced RNAs containing SL1 [76]. It was proposed that binding of the Gag precursor is controlled through a mechanism of double regulation: the region 5′ of SL1, present on all viral RNAs, prevents binding of Gag to SL1, whilst a downstream region in the Gag gene, only present in the gRNA, abolishes this negative effect [13] (Figure 3A). This mechanism probably requires tertiary interactions that cooperate to build a high affinity Gag binding site, but these remain to be identified.


The Life-Cycle of the HIV-1 Gag – RNA Complex
RNA structural models proposed to regulate the packaging and translation of the gRNA. (A) Gag binding is subjected to a mechanism of double regulation. The region upstream of SL1 (present in all viral RNAs) negatively regulates Gag binding. A region upstream of SL1 prevents binding of Gag to SL1 and this negative effect is counteracted by a motif downstream of SL4, present only in gRNA species; (B) The Long Distance Interaction (LDI) proposed to promote translation and the Branched Multiple Hairpin (BMH) proposed to promote packaging; (C) The U5 region is involved in alternative interactions with the dimerization initiation site (DIS) (promoting translation) and the region surrounding the AUG start codon (promoting packaging). A three-way junction, which further extends the U5-AUG interaction and eliminates SL2, is proposed to favour packaging. TAR: Tat responsive element; Poly-A: polyadenylation signal, U5: unique 5′ region, PBS: primer binding site; SL: stem loop; DIS: dimerization initiation site; SD: splice donor; Psi: packaging signal; AUG; start codon.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035962&req=5

viruses-08-00248-f003: RNA structural models proposed to regulate the packaging and translation of the gRNA. (A) Gag binding is subjected to a mechanism of double regulation. The region upstream of SL1 (present in all viral RNAs) negatively regulates Gag binding. A region upstream of SL1 prevents binding of Gag to SL1 and this negative effect is counteracted by a motif downstream of SL4, present only in gRNA species; (B) The Long Distance Interaction (LDI) proposed to promote translation and the Branched Multiple Hairpin (BMH) proposed to promote packaging; (C) The U5 region is involved in alternative interactions with the dimerization initiation site (DIS) (promoting translation) and the region surrounding the AUG start codon (promoting packaging). A three-way junction, which further extends the U5-AUG interaction and eliminates SL2, is proposed to favour packaging. TAR: Tat responsive element; Poly-A: polyadenylation signal, U5: unique 5′ region, PBS: primer binding site; SL: stem loop; DIS: dimerization initiation site; SD: splice donor; Psi: packaging signal; AUG; start codon.
Mentions: HIV-1 packaging of the gRNA dimer is strongly favored over abundant cellular RNAs and viral spliced mRNA species. As previously described, the specific recognition motif for the Gag precursor was identified as the internal loop and distal helix of SL1 [13,68]. These results were unexpected as SL1 is located 5′ of the spliced donor site and is thus present both on the genomic and on the spliced viral RNAs, suggesting a mechanism preventing Gag binding to SL1 in spliced viral RNA. Consistent with this idea, SL1 promotes exclusively the packaging of the unspliced gRNA, whereas spliced viral RNAs deleted for SL1 are incorporated with equal efficiency as spliced RNAs containing SL1 [76]. It was proposed that binding of the Gag precursor is controlled through a mechanism of double regulation: the region 5′ of SL1, present on all viral RNAs, prevents binding of Gag to SL1, whilst a downstream region in the Gag gene, only present in the gRNA, abolishes this negative effect [13] (Figure 3A). This mechanism probably requires tertiary interactions that cooperate to build a high affinity Gag binding site, but these remain to be identified.

View Article: PubMed Central - PubMed

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) replication is a highly regulated process requiring the recruitment of viral and cellular components to the plasma membrane for assembly into infectious particles. This review highlights the recent process of understanding the selection of the genomic RNA (gRNA) by the viral Pr55Gag precursor polyprotein, and the processes leading to its incorporation into viral particles.

No MeSH data available.