The Native Structure of the Human Immunodeficiency Virus Type 1 RNA Genome Is Required for the First Strand Transfer of Reverse Transcription

Berkhout, Ben; Das, Atze T.; Wamel, Jeroen L.B. van

doi:10.1006/viro.1998.9321

Cited by 30 publications

(28 citation statements)

References 45 publications

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“…These results seem to indicate that the inserted fragment of the mutant caused an abnormal secondary or tertiary structure of the overall viral RNA genome, resulting in poor reverse transcription. Viral genome dimerization and/or DIS was reported to play a role in efficient reverse transcription (6,29), and our data supported these earlier arguments.…”

Section: Discussionsupporting

confidence: 90%

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

Shioda

2007

J Virol

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It has been suggested that the dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome plays an important role at various stages of the viral life cycle. Recently we found that the duplication of the DIS/DLS region on viral RNA caused the production of partially monomeric RNAs in virions, indicating that this region indeed mediates RNA-RNA interaction. In this report, we followed up on this finding to identify the necessary and sufficient region for RNA dimerization in the virion of HIV-1. The region thus identified was 144 bases in length, extending from the junction of R/U5 and U5/L stem-loops to the end of SL4. The trans-acting responsive element, polyadenylation signal, primer binding site, upper stem-loop of U5/L, and SL2 were not needed for the function of this region. The insertion of this region into the ectopic location of the viral genome did not affect the level of virion production by transfection. However, the resultant virions contained monomerized genomes and showed drastic reductions in infectivity. A reduction was observed especially in the reverse transcription process. An attempt to generate a replication-competent virus with monomerized genome was performed by the long-term culture of mutant virus-infected cells. All recovered viruses were wild-type revertants, indicating a fatal defect of the mutation. These results suggest that genome dimerization or DIS/DLS itself also plays an important role in the early stages of virus infection.

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Section: Discussionsupporting

confidence: 90%

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

Shioda

2007

J Virol

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“…The inability of these mutant HIV-1 RNA genomes to mature into more stable ED dimers may trigger subsequent defects, e.g. genome disintegration over time or incomplete reverse transcription as suggested previously (64). Our results indeed suggest a link between RNA dimer maturation and reverse transcription.…”

Section: Discussionsupporting

confidence: 81%

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

Bel

Das

Cornelissen

et al. 2014

Journal of Biological Chemistry

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Background: Retroviruses package a genomic RNA dimer. In vitro studies suggested kissing loop and extended dimer (ED) RNA-RNA interactions. Results: HIV-1 mutants with ED defects are replication-impaired, and revertant viruses with compensatory RNA mutations were selected. Conclusion: We describe a correlation between in vitro ED defects and poor virus replication. Significance: We present, to our knowledge, the first in vivo evidence for the importance of the ED.

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“…Furthermore, annealing of tRNA 3 Lys to the PBS does not inhibit HIV-1 RNA dimerization in vitro (59), indicating that the PBS is not required for the DIS-mediated HIV-1 RNA dimerization. Finally, deletion of the PBS does not impair RNA dimerization in vivo, and it does not affect the thermal stability of the dimer (60). Thus, the results obtained with HIV-1 indicate that the presence of a self-complementary sequence in the PBS is not sufficient for the PBS to be involved in RNA dimerization.…”

Section: Fig 7 Binding Of Trnamentioning

confidence: 87%

Identification of the in Vitro HIV-2/SIV RNA Dimerization Site Reveals Striking Differences with HIV-1

Jossinet¹,

Lodmell²,

Ehresmann

et al. 2001

Journal of Biological Chemistry

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Although their genomes cannot be aligned at the nucleotide level, the HIV-1/SIVcpz and the HIV-2/SIVsm viruses are closely related lentiviruses that contain homologous functional and structural RNA elements in their 5-untranslated regions. In both groups, the domains containing the trans-activating region, the 5-copy of the polyadenylation signal, and the primer binding site (PBS) are followed by a short stem-loop (SL1) containing a six-nucleotide self-complementary sequence in the loop, flanked by unpaired purines. In HIV-1, SL1 is involved in the dimerization of the viral RNA, in vitro and in vivo. Here, we tested whether SL1 has the same function in HIV-2 and SIVsm RNA. Surprisingly, we found that SL1 is neither required nor involved in the dimerization of HIV-2 and SIV RNA. We identified the NarI sequence located in the PBS as the main site of HIV-2 RNA dimerization. cis and trans complementation of point mutations indicated that this self-complementary sequence forms symmetrical intermolecular interactions in the RNA dimer and suggested that HIV-2 and SIV RNA dimerization proceeds through a kissing loop mechanism, as previously shown for HIV-1. Furthermore, annealing of tRNA 3Lys to the PBS strongly inhibited in vitro RNA dimerization, indicating that, in vivo, the intermolecular interaction involving the NarI sequence must be dissociated to allow annealing of the primer tRNA.

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The Native Structure of the Human Immunodeficiency Virus Type 1 RNA Genome Is Required for the First Strand Transfer of Reverse Transcription

Cited by 30 publications

References 45 publications

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

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

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

Identification of the in Vitro HIV-2/SIV RNA Dimerization Site Reveals Striking Differences with HIV-1

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