Minimal Region Sufficient for Genome Dimerization in the Human Immunodeficiency Virus Type 1 Virion and Its Potential Roles in the Early Stages of Viral Replication

Sakuragi, Jun-ichi; Sakuragi, Sayuri; Shioda, Tatsuo

doi:10.1128/jvi.00429-07

Cited by 34 publications

(47 citation statements)

References 44 publications

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“…However, once the regulation of Tat/TAR on transcription was replaced with a tetracycline-inducible system, it became apparent that the TAR hairpin is not required for packaging (Das et al, 2007). Further studies confirm that the TAR hairpin as well as the Poly(A) signal are dispensable for RNA dimerization and packaging (Heng et al, 2012; Sakuragi et al, 2007). …”

Section: The Rendezvous: Rna Partner Selection / Dimerization and Rnamentioning

confidence: 81%

Life of psi: How full-length HIV-1 RNAs become packaged genomes in the viral particles

et al. 2014

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As a member of the retrovirus family, HIV-1 packages its RNA genome into particles and replicates through a DNA intermediate that integrates into the host cellular genome. The multiple genes encoded by HIV-1 are expressed from the same promoter and their expression is regulated by splicing and ribosomal frameshift. The full-length HIV-1 RNA plays a central role in viral replication as it serves as the genome in the progeny virus and is used as the template for Gag and GagPol translation. In this review, we summarize findings that contribute to our current understanding of how full-length RNA is expressed and transported, cis- and trans-acting elements important for RNA packaging, the locations and timing of RNA:RNA and RNA:Gag interactions, and the processes required for this RNA to be packaged into viral particles.

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Section: The Rendezvous: Rna Partner Selection / Dimerization and Rnamentioning

confidence: 81%

Life of psi: How full-length HIV-1 RNAs become packaged genomes in the viral particles

et al. 2014

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“…′ -UTR dimerization in vitro or viral RNA packaging (Sakuragi et al 2007;Heng et al 2012;Sakuragi et al 2012). However, internal loops are known to introduce thermodynamic instability in the stems, and deleting the internal PBS loop could have a stabilizing effect on the lower region of the PBS stem, which has been reported to be important for dimerization and packaging of RNA (Sakuragi et al 2003(Sakuragi et al , 2012.…”

Section: Discussionmentioning

confidence: 99%

Annealing to sequences within the primer binding site loop promotes an HIV-1 RNA conformation favoring RNA dimerization and packaging

Seif

Niu

Kleiman

2013

RNA

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The 5 ′ untranslated region (5 ′ UTR) of HIV-1 genomic RNA (gRNA) includes structural elements that regulate reverse transcription, transcription, translation, tRNA Lys3 annealing to the gRNA, and gRNA dimerization and packaging into viruses. It has been reported that gRNA dimerization and packaging are regulated by changes in the conformation of the 5 ′ -UTR RNA. In this study, we show that annealing of tRNA Lys3 or a DNA oligomer complementary to sequences within the primer binding site (PBS) loop of the 5 ′ UTR enhances its dimerization in vitro. Structural analysis of the 5 ′ -UTR RNA using selective 2 ′ -hydroxyl acylation analyzed by primer extension (SHAPE) shows that the annealing promotes a conformational change of the 5 ′ UTR that has been previously reported to favor gRNA dimerization and packaging into virus. The model predicted by SHAPE analysis is supported by antisense experiments designed to test which annealed sequences will promote or inhibit gRNA dimerization. Based on reports showing that the gRNA dimerization favors its incorporation into viruses, we tested the ability of a mutant gRNA unable to anneal to tRNA Lys3 to be incorporated into virions. We found a ∼60% decrease in mutant gRNA packaging compared with wild-type gRNA. Together, these data further support a model for viral assembly in which the initial annealing of tRNA Lys3 to gRNA is cytoplasmic, which in turn aids in the promotion of gRNA dimerization and its incorporation into virions.

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“…We further examined the mechanism that regulates HIV-1 RNA genome packaging and found that two copies of viral RNAs are packaged regardless of whether the RNAs were 17 kb or 3 kb, indicating that HIV-1 RNA packaging is not regulated by the mass of the RNA genome (12). To examine whether HIV-1 RNA packaging is regulated by the recognition of two copies of RNA or one dimeric RNA, we engineered the HIV-1 genome to contain a second dimerization signal as previously described (13,14). The two dimerization sites in the same RNA molecule can interact to form a "self-dimer"; we found that in this case, only one copy of the RNA, or one "self-dimer," is packaged.…”

mentioning

confidence: 99%

Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

Dilley

Nikolaitchik

Galli

et al. 2017

J Virol

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Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.IMPORTANCE Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral RNA genome carries the genetic information to new host cells, providing instructions to generate new virions, and therefore is essential for virion infectivity. In this report, we show that the specific interaction of the viral RNA genome with the structural protein Gag facilitates virion assembly and particle production. These findings resolve the conundrum that HIV-1 RNA is selectively packaged into virions with high efficiency despite being dispensable for virion assembly. Understanding the mechanism used by HIV-1 to ensure genome packaging provides significant insights into viral assembly and replication.

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Minimal Region Sufficient for Genome Dimerization in the Human Immunodeficiency Virus Type 1 Virion and Its Potential Roles in the Early Stages of Viral Replication

Cited by 34 publications

References 44 publications

Life of psi: How full-length HIV-1 RNAs become packaged genomes in the viral particles

Life of psi: How full-length HIV-1 RNAs become packaged genomes in the viral particles

Annealing to sequences within the primer binding site loop promotes an HIV-1 RNA conformation favoring RNA dimerization and packaging

Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

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