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Cited by 39HIV Research and TreatmentT-cell and Retrovirus StudiesHIV/AIDS drug development and treatment

Inhibition of HIV-1 Gag–membrane interactions by specific RNAs

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Todd, Gabrielle C., Duchon, Alice, Inlora, Jingga, Olson, Erik D., Musier-Forsyth, Karin, Ono, Akira·2017·RNA
DOI 10.1261/rna.058453.116PMC PMC5311501
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Abstract

HIV-1 particle assembly, which occurs at the plasma membrane (PM) of cells, is driven by the viral polyprotein Gag. Gag recognizes phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P 2], a PM-specific phospholipid, via the highly basic region (HBR) in its N-terminal matrix (MA) domain. The HBR is also known to bind to RNA. We have previously shown, using an in vitro liposome binding assay, that RNA inhibits Gag binding to membranes that lack PI(4,5)P 2. If this RNA block is removed by RNase treatment, Gag can bind nonspecifically to other negatively charged membranes. In an effort to identify the RNA species that confer this inhibition of Gag membrane binding, we have tested the impact of purified RNAs on Gag interactions with negatively charged liposomes lacking PI(4,5)P 2. We found that some tRNA species and RNAs containing stem–loop 1 of the psi region in the 5′ untranslated region of the HIV-1 genome impose inhibition of Gag binding to membranes lacking PI(4,5)P 2. In contrast, a specific subset of tRNAs, as well as an RNA sequence previously selected in vitro for MA binding, failed to suppress Gag–membrane interactions. Furthermore, switching the identity of charged residues in the HBR did not diminish the susceptibility of Gag–liposome binding for each of the RNAs tested, while deletion of most of the NC domain abrogates the inhibition of membrane binding mediated by the RNAs that are inhibitory to WT Gag–liposome binding. These results support a model in which NC facilitates binding of RNA to MA and thereby promotes RNA-based inhibition of Gag–membrane binding.

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  • A model was proposed wherein NC loads the tRNA onto MA as a prerequisite.

    “A model was proposed wherein NC “loads” the tRNA onto MA as a prerequisite (81).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [81]

    The Results section hypothesizes that RNA binding to NC promotes RNA binding to MA, which supports the proposed ‘loading’ model. But the Discussion says NC could instead affect MA–RNA interactions indirectly through Gag conformation, and reports that deleting NC did not significantly change which tRNAs bound MA in cells. The paper therefore does not establish NC loading as a prerequisite. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • The NC domain is required for the RNA-mediated effects on Gag-membrane binding.

    “Moreover, the NC domain was required for the RNA-mediated effects on Gag-membrane binding.”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [81]

  • tRNA Pro, but not tRNA Lys,3, is among the RNA species able to inhibit Gag membrane binding in vitro.

    “Interestingly, tRNA Pro , but not tRNA Lys,3 , is among the RNA species able to inhibit Gag membrane binding in vitro.”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [81]

  • tRNA plays a regulatory role in Gag membrane binding.

    “tRNA plays a regulatory role in Gag membrane binding.”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [81]

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Cited by

Sorted by citations

Authors
Todd, G. C., Duchon, A., Inlora, J., Olson, E. D., Musier-Forsyth, K., & Ono, A.
Affiliations
  • University of Michigan (US)
  • The Ohio State University (US)
Corresponding author
Ono, Akira
ORCID
Venue
RNA
Publisher
Cold Spring Harbor Laboratory
Published
2016-12-08
Volume
23
Issue
3
Pages
395-405
ISSN
  • 1355-8382 (ISSN-L)
  • 1469-9001
DOI
10.1261/rna.058453.116
PMC
PMC5311501
OpenAlex
W2560258370
Cited by
39
References
5
Citations by year
2024: 4 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 7 · 2016: 1
FWCI
3.00
Type
journal article
Language
en
Open access
Locations
  • RNA (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (T32 AI007527)
  • American Heart Association (13PRE17060006)
  • University of Michigan
  • NIH (T32 GM008512, F31 AI120868, R01 GM 065056, R01 AI071727)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1 Gag, matrix domain, phosphatidylinositol 4,5-bisphosphate, RNA binding, tRNA, 5' untranslated region, nucleocapsid domain, liposome binding
MeSH terms
Base Sequence, Binding Sites, Cell Membrane, Cloning, Molecular, Escherichia coli, Humans, Liposomes, Nucleic Acid Conformation, Protein Binding, Recombinant Proteins, RNA, Transfer, Saccharomyces cerevisiae, HIV-1, Gene Expression, Phosphatidylinositol 4,5-Diphosphate, Base Pairing, Aptamers, Nucleotide, gag Gene Products, Human Immunodeficiency Virus, Static Electricity

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