ArticleProceedings of the National Academy of Sciences of the United States of America2000
Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
187 citing papers in PubMed, 337 citations in OpenAlex.
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- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
- The role of post-translational modifications in parvovirus life cycle.Frontiers in veterinary science · 2025Review
- Functional 20S Proteasomes in Retroviruses: Evidence in Favor.International journal of molecular sciences · 2024Article
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- Multiple functions of the nonstructural protein 3D in picornavirus infection.Frontiers in immunology · 2024Review
- Lipid-anchored proteasomes control membrane protein homeostasis.Science advances · 2023Article
- The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry.Viruses · 2023Article
- Facile hermetic TEM grid preparation for molecular imaging of hydrated biological samples at room temperature.Nature communications · 2023Article
- The Involvement of Ubiquitination and SUMOylation in Retroviruses Infection and Latency.Viruses · 2023Review
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- Influenza A Virus Uses PSMA2 for Downregulation of the NRF2-Mediated Oxidative Stress Response.Journal of virology · 2022Article
- Single center, open label dose escalating trial evaluating once weekly oral ixazomib in ART-suppressed, HIV positive adults and effects on HIV reservoir size in vivo.EClinicalMedicine · 2021Article
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- Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role.International journal of molecular sciences · 2021Review
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- Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
127 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Retrovirus assembly and maturation involve folding and transport of viral proteins to the virus assembly site followed by subsequent proteolytic cleavage of the Gag polyprotein within the nascent virion. We report that inhibiting proteasomes severely decreases the budding, maturation, and infectivity of HIV. Although processing of the Env glycoproteins is not changed, proteasome inhibitors inhibit processing of Gag polyprotein by the viral protease without affecting the activity of the HIV-1 viral protease itself, as demonstrated by in vitro processing of HIV-1 Gag polyprotein Pr55. Furthermore, this effect occurs independently of the virus release function of the HIV-1 accessory protein Vpu and is not limited to HIV-1, as proteasome inhibitors also reduce virus release and Gag processing of HIV-2. Electron microscopy analysis revealed ultrastructural changes in budding virions similar to mutants in the late assembly domain of p6(gag), a C-terminal domain of Pr55 required for efficient virus maturation and release. Proteasome inhibition reduced the level of free ubiquitin in HIV-1-infected cells and prevented monoubiquitination of p6(gag). Consistent with this, viruses with mutations in PR or p6(gag) were resistant to detrimental effects mediated by proteasome inhibitors. These results indicate the requirement for an active proteasome/ubiquitin system in release and maturation of infectious HIV particles and provide a potential pharmaceutical strategy for interfering with retrovirus replication.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.