Specific recognition of the HIV-1 genomic RNA by the Gag precursor
Open accessAbstract
During assembly of HIV-1 particles in infected cells, the viral Pr55(Gag) protein (or Gag precursor) must select the viral genomic RNA (gRNA) from a variety of cellular and viral spliced RNAs. However, there is no consensus on how Pr55(Gag) achieves this selection. Here, by using RNA binding and footprinting assays, we demonstrate that the primary Pr55(Gag) binding site on the gRNA consists of the internal loop and the lower part of stem-loop 1 (SL1), the upper part of which initiates gRNA dimerization. A double regulation ensures specific binding of Pr55(Gag) to the gRNA despite the fact that SL1 is also present in spliced viral RNAs. The region upstream of SL1, which is present in all HIV-1 RNAs, prevents binding to SL1, but this negative effect is counteracted by sequences downstream of SL4, which are unique to the gRNA.
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In HIV-1, HIV-2, HTLV-1, SIV, MMTV, and MPMV, single-stranded purine or unpaired stretches are critical for gRNA packaging, with mutational disruption leading to impaired Gag binding and gRNA packaging.
“in HIV-1, HIV-2, HTLV-1, SIV, MMTV, and MPMV, single-stranded purine or unpaired stretches are critical for gRNA packaging, with mutational disruption leading to impaired Gag binding and gRNA packaging”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Abd El-Wahab et al. 2014
Full-length Gag preferentially binds to a G//AGG loop in SL1, rather than the GGAG tetraloop in SL3.
“the full-length Gag was shown to preferentially bind to a G//AGG loop in SL1, rather than the GGAG tetraloop in SL3”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Abd El-Wahab et al. 2014
The Gag polyprotein first selectively recognizes gRNA amongst a variety of cellular and spliced viral RNAs, and such RNA-Gag binding favors Gag multimerization.
“The Gag polyprotein first selectively recognizes gRNA amongst a variety of cellular and spliced viral RNAs, and such RNA–Gag binding favors Gag multimerization”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Abd El-Wahab et al. 2014
Cites
How retroviruses select their genomes
D'Souza, V., & Summers, M. F. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1210 · Cited by 339 · see citing works
Paillart, J. C., Marquet, R., Skripkin, E., Ehresmann, B., & Ehresmann, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47011-1 · Cited by 201 · see citing works
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Importance of viral late domains in budding and release of enveloped RNA viruses
Welker, L., Paillart, J.-C., & Bernacchi, S. (2021) · Viruses · doi:10.3390/v13081559 · Cited by 36 · see citing works
Self-citationChameettachal, A., Pillai, V. N., Ali, L. M., Pitchai, F. N. N., Ardah, M. T., Mustafa, F., Marquet, R., & Rizvi, T. A. (2018) · Viruses · doi:10.3390/v10060334 · Cited by 13 · see citing works
Self-citationPillai, V. N., Ali, L. M., Prabhu, S. G., Krishnan, A., Tariq, S., Mustafa, F., & Rizvi, T. A. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e12892 · Cited by 4 · see citing works
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
- Authors
- Abd El-Wahab, E. W., Smyth, R. P., Mailler, E., Bernacchi, S., Vivet-Boudou, V., Hijnen, M., Jossinet, F., Mak, J., Paillart, J.-C., & Marquet, R.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Burnet Institute (AU)
- Australian Centre for Disease Preparedness (AU)
- Corresponding author
- Paillart, Jean-Christophe
- Marquet, Roland
- ORCID
- Venue
- Nature Communications
- Published
- 2014-07-02
- Volume
- 5
- Issue
- 1
- Pages
- 4304-4304
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1984642176
- Cited by
- 123
- References
- 2
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 15 · 2021: 15 · 2020: 12 · 2019: 9 · 2018: 16 · 2017: 9 · 2016: 17 · 2015: 6 · 2014: 2
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion)
- univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion, cc-by)
- Funders
- Styrelsen för Internationellt Utvecklingssamarbete
- Sidaction
- Agence Nationale de la Recherche
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- HIV-1, Pr55gag, Gag precursor, viral RNA genome, RNA binding sites, RNA dimerization, viral RNA recognition, viral assembly, RNA footprinting
- MeSH terms
- Binding Sites, Protein Precursors, RNA, Viral, HIV-1, Genome, Viral, Virus Assembly
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