ArticleJournal of virology2016
Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74.
Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 88 citations in OpenAlex.
- Lenacapavir allosterically remodels the HIV-1 capsid.Science advances · 2026Article
- Capsid stabilization reprograms the nuclear fate of the HIV genome.Science advances · 2026Article
- Discovery of 4-Quinazolinone-Containing Phenylalanine Derivatives as Potent, Resistant-Tolerant HIV Capsid Inhibitors.MedComm · 2026Article
- HIV-1 uncoating location dictates sites of integration.Nature communications · 2026Article
- Damaging the conical morphology of HIV-1 capsid by targeting the FG-binding pocket and disfavoring pentameric subunits needed for core closure.bioRxiv : the preprint server for biology · 2026Article
- The host protein cyclophilin A restricts nuclear entry of HIV-1 mutants by reducing the elasticity of the viral capsid.PLoS pathogens · 2026Article
- Structural, biophysical, and virological mechanistic characterization of HIV-1 capsid-targeting antivirals.bioRxiv : the preprint server for biology · 2025Article
- Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging.Nature communications · 2025Article
- New Advances in Anti-HIV-1 Strategies Targeting the Assembly and Stability of Capsid Protein.International journal of molecular sciences · 2025Review
- Overview of host-directed antiviral targets for future research and drug development.Acta pharmaceutica Sinica. B · 2025Review
- Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025Review
- A new class of capsid-targeting inhibitors that specifically block HIV-1 nuclear import.EMBO molecular medicine · 2024Article
- The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.PLoS pathogens · 2024Article
- Elasticity of the HIV-1 core facilitates nuclear entry and infection.PLoS pathogens · 2024Article
- A Branched SELEX Approach Identifies RNA Aptamers That Bind Distinct HIV-1 Capsid Structural Components.ACS infectious diseases · 2024Article
- Design and Synthesis of New GS-6207 Subtypes for Targeting HIV-1 Capsid Protein.International journal of molecular sciences · 2024Article
- Article
- HIV-1 capsid and viral DNA integration.mBio · 2024Review
- 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
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledThe viral capsid of HIV-1 interacts with a number of host factors to orchestrate uncoating and regulate downstream events, such as reverse transcription, nuclear entry, and integration site targeting. PF-3450074 (PF74), an HIV-1 capsid-targeting low-molecular-weight antiviral compound, directly binds to the capsid (CA) protein at a site also utilized by host cell proteins CPSF6 and NUP153. Here, we found that the dose-response curve of PF74 is triphasic, consisting of a plateau and two inhibitory phases of different slope values, consistent with a bimodal mechanism of drug action. High PF74 concentrations yielded a steep curve with the highest slope value among different classes of known antiretrovirals, suggesting a dose-dependent, cooperative mechanism of action. CA interactions with both CPSF6 and cyclophilin A (CypA) were essential for the unique dose-response curve. A shift of the steep curve at lower drug concentrations upon blocking the CA-CypA interaction suggests a protective role for CypA against high concentrations of PF74. These findings, highlighting the unique characteristics of PF74, provide a model in which its multimodal mechanism of action of both noncooperative and cooperative inhibition by PF74 is regulated by interactions of cellular proteins with incoming viral capsids. IMPORTANCE: PF74, a novel capsid-targeting antiviral against HIV-1, shares its binding site in the viral capsid protein (CA) with the host factors CPSF6 and NUP153. This work reveals that the dose-response curve of PF74 consists of two distinct inhibitory phases that are differentially regulated by CA-interacting host proteins. PF74's potency depended on these CA-binding factors at low doses. In contrast, the antiviral activity of high PF74 concentrations was attenuated by cyclophilin A. These observations provide novel insights into both the mechanism of action of PF74 and the roles of host factors during the early steps of HIV-1 infection.
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Registered trials
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.