ArticleRetrovirology2013
The NTD-CTD intersubunit interface plays a critical role in assembly and stabilization of the HIV-1 capsid.
Article in Retrovirology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 56 citations in OpenAlex.
- HIV capsid inhibitors: Mechanisms, resistance, and therapeutic advances.PLoS pathogens · 2026Review
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- The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.PLoS pathogens · 2024Article
- A Branched SELEX Approach Identifies RNA Aptamers That Bind Distinct HIV-1 Capsid Structural Components.ACS infectious diseases · 2024Article
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- Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus.Journal of virology · 2023Review
- The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.bioRxiv : the preprint server for biology · 2023Article
- HIV-1 capsid stability enables inositol phosphate-independent infection of target cells and promotes integration into genes.PLoS pathogens · 2023Article
- PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome.bioRxiv : the preprint server for biology · 2023Article
- Discovery and Mechanistic Investigation of Piperazinone Phenylalanine Derivatives with Terminal Indole or Benzene Ring as Novel HIV-1 Capsid Modulators.Molecules (Basel, Switzerland) · 2022Article
- Inhibition of HIV-1 replication using the CRISPR/cas9-no NLS system as a prophylactic strategy.Heliyon · 2022Article
- Selection and identification of an RNA aptamer that specifically binds the HIV-1 capsid lattice and inhibits viral replication.Nucleic acids research · 2022Article
- Changes in dynamic and static structures of the HIV-1 p24 capsid protein N-domain caused by amino-acid substitution are associated with its viral viability.Protein science : a publication of the Protein Society · 2021Article
- HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules.Retrovirology · 2021Review
- HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration.PLoS pathogens · 2021Article
- Structure, Function, and Interactions of the HIV-1 Capsid Protein.Life (Basel, Switzerland) · 2021Review
- Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells.PLoS pathogens · 2021Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundLentiviruses exhibit a cone-shaped capsid composed of subunits of the viral CA protein. The intrinsic stability of the capsid is critical for HIV-1 infection, since both stabilizing and destabilizing mutations compromise viral infectivity. Structural studies have identified three intersubunit interfaces in the HIV-1 capsid, two of which have been previously studied by mutational analysis. In this present study we analyzed the role of a third interface, that which is formed between the amino terminal domain (NTD) and carboxyl terminal domain (CTD) of adjacent subunits.
resultsWe provided evidence for the presence of the NTD-CTD interface in HIV-1 particles by engineering intersubunit NTD-CTD disulfide crosslinks, resulting in accumulation of disulfide-linked oligomers up to hexamers. We also generated and characterized a panel of HIV-1 mutants containing substitutions at this interface. Some mutants showed processing defects and altered morphology from that of wild type, indicating that the interface is important for capsid assembly. Analysis of these mutants by transmission electron microscopy corroborated the importance of this interface in assembly. Other mutants exhibited quantitative changes in capsid stability, many with unstable capsids, and one mutant with a hyperstable capsid. Analysis of the mutants for their capacity to saturate TRIMCyp-mediated restriction in trans confirmed that the unstable mutants undergo premature uncoating in target cells. All but one of the mutants were markedly attenuated in replication owing to impaired reverse transcription in target cells.
conclusionsOur results demonstrate that the NTD-CTD intersubunit interface is present in the mature HIV-1 capsid and is critical for proper capsid assembly and stability.
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