Maintenance of the Gag/Gag-Pol Ratio Is Important for Human Immunodeficiency Virus Type 1 RNA Dimerization and Viral Infectivity

Shehu-Xhilaga, Miranda; Crowe, Suzanne; Mak, Johnson

doi:10.1128/jvi.75.4.1834-1841.2001

Cited by 210 publications

(246 citation statements)

References 42 publications

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“…As the observed splicing was only partial in all tissues tested ( Figure 2C), it can be assumed that the gag-prot product is generally overproduced compared to rt/rh-int. Thus, splicing appears to be an alternative mechanism to the stop codon misreading or ribosomal frameshift which provides regulation of gag to gag-pol (prot-rt/rh-int) transcript ratios in some retroelements (Swanstrom and Wills, 1997;Vogt et al, 1997;Shehu-Xhilaga et al, 2001, and references therein).…”

Section: Discussionmentioning

confidence: 99%

Highly abundant pea LTR retrotransposon Ogre is constitutively transcribed and partially spliced

2003

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We have isolated and characterized a novel giant retroelement, named Ogre, which is over 22 kb long and makes up at least 5% of the pea (Pisum sativum L.) genome. This element can be classified as a Ty3/gypsy-like LTR retrotransposon based on the presence of long terminal repeats (LTRs) and the order of the domains coding for typical retrotransposon proteins. In addition to its extreme length, it has several features which make it unique among the retroelements described so far: (1) the sequences coding for gag and prot proteins are separated from the rt/rh-int domains by several stop codons; (2) the region containing these stop codons is removed from the element transcripts by splicing which results in reconstitution of the complete gag-pol coding sequence; (3) only a part of the transcripts is spliced which probably determines the ratio of translated proteins; (4) the element contains an extra ORF located upstream the gag-pol coding sequences, potentially coding for a protein of 546-562 amino acids with unknown function. The transcriptional activity of the Ogre elements has been detected in all organs tested (leaves, roots, flowers) as well as in wounded leaves and protoplasts. Considering this retroelement's constitutive expression and observed high mutual similarity of the element genomic sequences, it is possible to speculate about its recent amplification in the genomes of pea and other legume plants.

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Section: Discussionmentioning

confidence: 99%

Highly abundant pea LTR retrotransposon Ogre is constitutively transcribed and partially spliced

2003

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“…The Gag-Pol to Gag ratio in HIV-1 is critical for the RNA dimerization, particle assembly, replication, and viral infectivity (Park and Morrow 1991;Karacostas et al 1993;Shehu-Xhilaga et al 2001), which suggests that altering the frameshift efficiency could affect viral replication. So far, the frameshift efficiency has only been studied for subtype B of HIV-1 group M. However, the development of an antiviral strategy directed against frameshifting requires the characterization of the frameshift efficiency of the other subtypes.…”

Section: Introductionmentioning

confidence: 99%

Efficiency of a programmed −1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M

Baril

Dulude²,

Gendron³

et al. 2003

RNA

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The synthesis of the Gag-Pol polyprotein, the precursor of the enzymes of the human immunodeficiency virus type 1 (HIV-1), requires a programmed −1 ribosomal frameshift. This frameshift has been investigated so far only for subtype B of HIV-1 group M. In this subtype, the frameshift stimulatory signal was found to be a two-stem helix, in which a three-purine bulge interrupts the two stems. In this study, using a luciferase reporter system, we compare, for the first time, the frameshift efficiency of all the subtypes of group M. Mutants of subtype B, including a natural variant were also investigated. Our results with mutants of subtype B confirm that the bulge and the lower stem of the frameshift stimulatory signal contribute to the frameshift in addition to the upper stem-loop considered previously as the sole participant. Our results also show that the frameshift stimulatory signal of all of the other subtypes of group M can be folded into the same structure as in subtype B, despite sequence variations. Moreover, the frameshift efficiency of these subtypes, when assessed in cultured cells, falls within a narrow window (the maximal deviation from the mean value calculated from the experimental values of all the subtypes being ∼35%), although the predicted thermodynamic stability of the frameshift stimulatory signal differs between the subtypes (from −17.2 kcal/mole to −26.2 kcal/mole). The fact that the frameshift efficiencies fall within a narrow range for all of the subtypes of HIV-1 group M stresses the potential of the frameshift event as an antiviral target.

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“…The production of Gag-Pol is likely important for packaging the Pol products within the particle. Furthermore, the level of Pol relative to Gag is critical for retroelement viability because particle assembly requires many more copies of Gag than Pol (Park and Morrow 1991;Karacostas et al 1993;Shehu-Xhilaga et al 2001;Telenti et al 2002), and therefore Pol is typically expressed at the translational level through deviations from standard decoding mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Translational recoding signals between gag and pol in diverse LTR retrotransposons

Gao

Havecker

Baranov

et al. 2003

RNA

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Because of their compact genomes, retroelements (including retrotransposons and retroviruses) employ a variety of translational recoding mechanisms to express Gag and Pol. To assess the diversity of recoding strategies, we surveyed gag/pol gene organization among retroelements from diverse host species, including elements exhaustively recovered from the genome sequences of Caenorhabditis elegans, Drosophila melanogaster, Schizosaccharomyces pombe, Candida albicans, and Arabidopsis thaliana. In contrast to the retroviruses, which typically encode pol in the −1 frame relative to gag, nearly half of the retroelements surveyed encode a single gag-pol open reading frame. This was particularly true for the Ty1/copia group retroelements. Most animal Ty3/gypsy retroelements, on the other hand, encode gag and pol in separate reading frames, and likely express Pol through +1 or −1 frameshifting. Conserved sequences conforming to slippery sites that specify viral ribosomal frameshifting were identified among retroelements with pol in the −1 frame. None of the plant retroelements encoded pol in the −1 frame relative to gag; however, two closely related plant Ty3/gypsy elements encode pol in the +1 frame. Interestingly, a group of plant Ty1/copia retroelements encode pol either in a +1 frame relative to gag or in two nonoverlapping reading frames. These retroelements have a conserved stem-loop at the end of gag, and likely express pol either by a novel means of internal ribosomal entry or by a bypass mechanism.

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Maintenance of the Gag/Gag-Pol Ratio Is Important for Human Immunodeficiency Virus Type 1 RNA Dimerization and Viral Infectivity

Cited by 210 publications

References 42 publications

Highly abundant pea LTR retrotransposon Ogre is constitutively transcribed and partially spliced

Highly abundant pea LTR retrotransposon Ogre is constitutively transcribed and partially spliced

Efficiency of a programmed −1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M

Translational recoding signals between gag and pol in diverse LTR retrotransposons

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