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In virio SHAPE analysis of tRNALys3 annealing to HIV-1 genomic RNA in wild type and protease-deficient virus

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Seif, Elias, Niu, Meijuan, Kleiman, Lawrence·2015·Retrovirology
DOI 10.1186/s12977-015-0171-7PMC PMC4445796
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Abstract

BACKGROUND: tRNA(Lys3) annealing to the viral RNA of human immunodeficiency virus type-1 (HIV-1) is an essential step in the virus life cycle, because this tRNA serves as the primer for initiating reverse transcription. tRNA(Lys3) annealing to viral RNA occurs in two steps. First, Gag promotes annealing of tRNA(Lys3) to the viral RNA during cytoplasmic HIV-1 assembly. Second, mature nucleocapsid (NCp7), produced from the processing of Gag by viral protease during viral budding from the cell, remodels the annealed complex to form a more stable interaction between the viral RNA and tRNA(Lys3), resulting in a more tightly bound and efficient primer for reverse transcription. RESULTS: In this report, we have used in virio SHAPE analysis of both the 5´-untranslated region in HIV-1 RNA and the annealed tRNA(Lys3) to determine structural differences of the annealed complex that occur between protease-negative (Pr-) and wild type viruses. Our results indicate that the weaker binding of tRNA(Lys3) annealed by Gag in Pr- virions reflects both missing interactions of tRNA(Lys3) with viral RNA regions in the upper PBS stem, and a weaker interaction with the internal stem-loop found within the unannealed primer binding site in viral RNA. CONCLUSIONS: We propose secondary structure models for the tRNA(Lys3)/viral RNA annealed complexes in PR- and wild type viruses that support the two-step annealing model by showing that Gag promotes a partial annealing of tRNA(Lys3) to HIV-1 viral RNA, followed by a more complete annealing by NCp7.

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  • A multistaged tRNA primer annealing process has been proposed wherein initial annealing by Gag is followed by more optimized annealing by NC in mature virions.

    “A multistaged tRNA primer annealing process has been proposed, wherein initial annealing by Gag is followed by more optimized annealing by NC in mature virions (45,46), a model further supported by in virio RNA structure-probing analysis (47).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [47]

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Cited by

Sorted by citations

Authors
Seif, E., Niu, M., & Kleiman, L.
Affiliations
Jewish General Hospital (CA)
Corresponding author
Kleiman, Lawrence
Venue
Retrovirology
Publisher
Springer Science and Business Media LLC
Published
2015-05-16
Volume
12
Issue
1
Pages
40-40
ISSN
1742-4690 (ISSN-L)
DOI
10.1186/s12977-015-0171-7
PMC
PMC4445796
OpenAlex
W1481261513
Cited by
36
References
5
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 1
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Retrovirology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (HOP 81389)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1, primer annealing, reverse transcription, Gag, NCp7, viral RNA secondary structure, 5' untranslated region, primer binding site
MeSH terms
Humans, Models, Molecular, Nucleic Acid Conformation, RNA, Transfer, Lys, RNA, Viral, HIV-1, HIV Protease, 5' Untranslated Regions, gag Gene Products, Human Immunodeficiency Virus

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