ArticleNucleic acids research1997
Forced evolution of a regulatory RNA helix in the HIV-1 genome.
Article in Nucleic acids research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Role of RNA structural plasticity in modulating HIV-1 genome packaging and translation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- HIV-1 tolerates changes in A-count in a small segment of the pol gene.Retrovirology · 2017Article
- A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal.Viruses · 2016Article
- Structural Insights into the HIV-1 Minus-strand Strong-stop DNA.The Journal of biological chemistry · 2016Article
- Progress and outlook in structural biology of large viral RNAs.Virus research · 2014Review
- Strong epistatic selection on the RNA secondary structure of HIV.PLoS pathogens · 2014Article
- Lysis delay and burst shrinkage of coliphage T7 by deletion of terminator Tφ reversed by deletion of early genes.Journal of virology · 2014Article
- Evolutionary biochemistry: revealing the historical and physical causes of protein properties.Nature reviews. Genetics · 2013Review
- Influence of genome-scale RNA structure disruption on the replication of murine norovirus--similar replication kinetics in cell culture but attenuation of viral fitness in vivo.Nucleic acids research · 2013Article
- Site-selective probing of cTAR destabilization highlights the necessary plasticity of the HIV-1 nucleocapsid protein to chaperone the first strand transfer.Nucleic acids research · 2013Article
- Specific temperature-induced perturbations of secondary mRNA structures are associated with the cold-adapted temperature-sensitive phenotype of influenza A virus.RNA biology · 2012Article
- Nonhistone protein acetylation as cancer therapy targets.Expert review of anticancer therapy · 2010Review
- Pausing during reverse transcription increases the rate of retroviral recombination.Journal of virology · 2006Article
- Structural features in the HIV-1 repeat region facilitate strand transfer during reverse transcription.RNA (New York, N.Y.) · 2001Article
- Repair of a Rev-minus human immunodeficiency virus type 1 mutant by activation of a cryptic splice site.Journal of virology · 2001Article
- Two alternating structures of the HIV-1 leader RNA.RNA (New York, N.Y.) · 2001Article
- A structured RNA motif is involved in correct placement of the tRNA(3)(Lys) primer onto the human immunodeficiency virus genome.Journal of virology · 2000Article
- A second-site mutation that restores replication of a Tat-defective human immunodeficiency virus.Journal of virology · 1999Article
- Genetic instability of live, attenuated human immunodeficiency virus type 1 vaccine strains.Journal of virology · 1999Article
- A hairpin structure in the R region of the human immunodeficiency virus type 1 RNA genome is instrumental in polyadenylation site selection.Journal of virology · 1999Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 5'and 3'end of the HIV-1 RNA genome forms a repeat (R) element that encodes a double stem-loop structure (the TAR and polyA hairpins). Phylogenetic analysis of the polyA hairpin in different human and simian immunodeficiency viruses suggests that the thermodynamic stability of the helix is fine-tuned. We demonstrated previously that mutant HIV-1 genomes with a stabilized or destabilized hairpin are severely replication-impaired. In this study, we found that the mutant with a destabilized polyA hairpin structure is conditionally defective. Whereas reduced replication is measured in infections at the regular temperature (37 degrees C), this mutant is more fit than the wild-type virus at reduced temperature (33 degrees C). This observation of a temperature-dependent replication defect underscores that the stability of this RNA structure is critical for function. An extensive analysis of revertant viruses was performed to further improve the understanding of the critical sequence and structural features of the element under scrutiny. The virus mutants with a stabilized or destabilized hairpin were used as a starting point in multiple, independent selections for revertant viruses with compensatory mutations. Both mutants reverted to hairpins with wild-type stability along various pathways by acquisition of compensatory mutations. We identified 19 different revertant HIV-1 forms with improved replication characteristics, providing a first look at some of the peaks in the total sequence landscape that are compatible with virus replication. These experiments also highlight some general principles of RNA structure building.
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