A Short Sequence Upstream of the 5′ Major Splice Site Is Important for Encapsidation of HIV-1 Genomic RNA

Kim, Hong-Jin; K, Liu; O’Rear, Julian J.

doi:10.1006/viro.1994.1037

Cited by 66 publications

(66 citation statements)

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“…In this study, we used 4 antisense sequences known to have anti-HIV-1 activity in either phosphorothioate (PS-ODN) or unmodified (PO-ODN) form: antisenses DIS and Pac, which are complementary to a portion of the 5'-long terminal repeat of the HIV-1 genome and are considered to be essential for HIV-1 RNA encapsidation 16,17 ; antisense GEM 91 (gene expression modulator 91), a 25-mer complement to the gag initiation site of HIV-1 18 ; and antisense rev, a 28-mer complementary to the 5'-end sequence of HIV-1 rev mRNA. 19 The ODN sequences are shown in Table 1.…”

Section: Antisense and Control Odnsmentioning

confidence: 99%

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

et al. 2002

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Section: Antisense and Control Odnsmentioning

confidence: 99%

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

et al. 2002

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“…Nevertheless, studies with mutant virions have indicated that the in vivo situation is much more complex, suggesting the possibility of multiple accessory dimerization signals (6,21,38). The ⌿ hairpin has been implicated as the core element that mediates packaging, but there is ample evidence for the involvement of additional sequence elements (25,28). It has also been suggested that the process of RNA dimerization may be coupled to RNA encapsidation; such a coupling seems to be an elegant mechanism for ensuring that only dimeric RNA genomes are packaged (18).…”

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confidence: 99%

A Riboswitch Regulates RNA Dimerization and Packaging in Human Immunodeficiency Virus Type 1 Virions

Ooms

Huthoff

Russell

et al. 2004

J Virol

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The genome of retroviruses, including human immunodeficiency virus type 1 (HIV-1), consists of two identical RNA strands that are packaged as noncovalently linked dimers. The core packaging and dimerization signals are located in the downstream part of the untranslated leader of HIV-1 RNA-the ⌿ and the dimerization initiation site (DIS) hairpins. The HIV-1 leader can adopt two alternative conformations that differ in the presentation of the DIS hairpin and consequently in their ability to dimerize in vitro. The branched multiple-hairpin (BMH) structure folds the poly(A) and DIS hairpins, but these domains are base paired in a long distance interaction (LDI) in the most stable LDI conformation. This LDI-BMH riboswitch regulates RNA dimerization in vitro. It was recently shown that the ⌿ hairpin structure is also presented differently in the LDI and BMH structures. Several detailed in vivo studies have indicated that sequences throughout the leader RNA contribute to RNA packaging, but how these diverse mutations affect the packaging mechanism is not known. We reasoned that these effects may be due to a change in the LDI-BMH equilibrium, and we therefore reanalyzed the structural effects of a large set of leader RNA mutations that were presented in three previous studies ( This analysis revealed a strict correlation between the status of the LDI-BMH equilibrium and RNA packaging. Furthermore, a correlation is apparent between RNA dimerization and RNA packaging, and these processes may be coordinated by the same LDI-BMH riboswitch mechanism.Retroviral particles package a dimeric RNA genome that is subsequently reverse transcribed into DNA by the virion-associated reverse transcriptase enzyme. The cis-acting RNA sequences and the trans-acting viral proteins that mediate RNA dimerization and RNA packaging have been studied extensively for several retroviruses, including human immunodeficiency virus type 1 (HIV-1) (9,20,35). It has proven particularly difficult to accurately map the RNA signals that execute these two processes, but most studies have indicated that these elements cluster within the untranslated leader region of the HIV-1 genome. In vitro studies have identified the dimerization initiation signal (DIS) as the primary dimerization signal, which acts through base pairing of a palindromic 6-nucleotide (nt) sequence motif in the exposed loop of the DIS hairpin (4,27,32,40). Nevertheless, studies with mutant virions have indicated that the in vivo situation is much more complex, suggesting the possibility of multiple accessory dimerization signals (6,21,38). The ⌿ hairpin has been implicated as the core element that mediates packaging, but there is ample evidence for the involvement of additional sequence elements (25,28). It has also been suggested that the process of RNA dimerization may be coupled to RNA encapsidation; such a coupling seems to be an elegant mechanism for ensuring that only dimeric RNA genomes are packaged (18).Huthoff and Berkhout demonstrated that the HIV-1 untranslated leader RNA can ado...

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“…The core ⌿ region in HIV-1, stem-loop 3 in the leader RNA, is immediately downstream of the major splice donor, upstream of the gag open reading frame (ORF), and thus present only on the viral genomic RNA. However, other RNA structures situated both upstream and downstream of the splice donor have roles in encapsidation, notably, the dimerization initiation site stem-loop, or stem-loop 1 (5,6,8,25,26,32,44).…”

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confidence: 99%

The Major Human Immunodeficiency Virus Type 2 (HIV-2) Packaging Signal Is Present on All HIV-2 RNA Species: Cotranslational RNA Encapsidation and Limitation of Gag Protein Confer Specificity

Griffin

Allen

Lever

2001

J Virol

121

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Deletion of a region of the human immunodeficiency virus type 2 (HIV-2) 5 leader RNA reduces genomic RNA encapsidation to about 5% that of wild-type virus with no defect in viral protein production but severely limits virus spread in Jurkat T cells, indicating that this region contains a major cis-acting encapsidation signal, or psi (⌿). Being upstream of the major splice donor, it is present on all viral transcripts. We have shown that HIV-2 selects its genomic RNA for encapsidation cotranslationally, rendering wild-type HIV-2 unable to encapsidate vector RNAs in trans . Virus with ⌿ deleted, however, encapsidates an HIV-2 vector, demonstrating competition for Gag protein. HIV-2 overcomes the lack of packaging signal location specificity by two novel mechanisms, cotranslational packaging and competition for limiting Gag polyprotein.

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A Short Sequence Upstream of the 5′ Major Splice Site Is Important for Encapsidation of HIV-1 Genomic RNA

Cited by 66 publications

References 0 publications

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

A Riboswitch Regulates RNA Dimerization and Packaging in Human Immunodeficiency Virus Type 1 Virions

The Major Human Immunodeficiency Virus Type 2 (HIV-2) Packaging Signal Is Present on All HIV-2 RNA Species: Cotranslational RNA Encapsidation and Limitation of Gag Protein Confer Specificity

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