ArticleRetrovirology2014
Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA.
Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 116 citations in OpenAlex.
- HIV capsid inhibitors: Mechanisms, resistance, and therapeutic advances.PLoS pathogens · 2026Review
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Stoichiometric binding of Cyclophilin-A to the HIV-1 capsid modulates its mechanoelastic properties.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
- CPSF6 promotes HIV-1 preintegration complex function.Journal of virology · 2025Article
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- Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025Review
- Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.PLoS pathogens · 2025Article
- The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.PLoS pathogens · 2025Article
- Cyclophilin A facilitates HIV-1 integration.Journal of virology · 2024Article
- HIV-1 usurps mixed-charge domain-dependent CPSF6 phase separation for higher-order capsid binding, nuclear entry and viral DNA integration.Nucleic acids research · 2024Article
- Role of Type I Interferons duringBiomolecules · 2024Review
- The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.bioRxiv : the preprint server for biology · 2024Article
- HIV-1 uncoating requires long double-stranded reverse transcription products.Science advances · 2024Article
- Capsid-dependent lentiviral restrictions.Journal of virology · 2024Review
- Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration.bioRxiv : the preprint server for biology · 2024Article
- Virus specificity and nucleoporin requirements for MX2 activity are affected by GTPase function and capsid-CypA interactions.PLoS pathogens · 2024Article
- HIV-1 capsid and viral DNA integration.mBio · 2024Review
- Cyclophilin inhibition as a strategy for the treatment of human disease.Frontiers in pharmacology · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe human peptidyl-prolyl isomerase Cyclophilin A (CypA) binds HIV-1 capsid (CA) and influences early steps in the HIV-1 replication cycle. The mechanism by which CypA regulates HIV-1 transduction efficiency is unknown. Disruption of CypA binding to CA, either by genetic means or by the competitive inhibitor cyclosporine A (CsA), reduces the efficiency of HIV-1 transduction in some cells but not in others. Transduction of certain cell types increases significantly when CypA binding to particular HIV-1 CA mutants, i.e., A92E, is prevented. Previous studies have suggested that this cell type-specific effect is due to a dominant-acting, CypA-dependent restriction factor.
resultsHere we investigated the mechanism by which CypA regulates HIV-1 transduction efficiency using 27 different human cell lines, 32 HeLa subclones, and several previously characterized HIV-1 CA mutants. Disruption of CypA binding to wild-type CA, or to any of the mutant CAs, caused a decrease in HIV-1 reverse transcription in all the cell lines analyzed here. This block to reverse transcription, though, did not correlate with cell type-specific effects on transduction efficiency. The level of 2-LTR circles, a marker for nuclear transport of the viral cDNA that results from reverse transcription, correlated closely with effects on infectivity. No correlation was observed between the cell type-specific effects on infectivity and the steady-state CypA protein levels in these cells. Instead, as indicated by a fate-of-capsid assay, CsA released the HIV-1 CA core from an apparent state of hyperstabilization, in a cell type-specific manner.
conclusionThese data demonstrate that, while CypA promotes reverse transcription under all conditions tested here, its effect on HIV-1 infectivity correlates more closely with effects on nuclear entry of the viral cDNA. The data also support the hypothesis that a cell-type specific CypA-dependent restriction factor blocks HIV-1 replication by delaying CA core uncoating and hindering nuclear entry.
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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.