ArticleeLife2020
MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
The trial behind it
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
16 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025Review
- Virus specificity and nucleoporin requirements for MX2 activity are affected by GTPase function and capsid-CypA interactions.PLoS pathogens · 2024Article
- Article
- Capsid-host interactions for HIV-1 ingress.Microbiology and molecular biology reviews : MMBR · 2023Review
- Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus.Journal of virology · 2023Review
- Virus specificity and nucleoporin requirements for MX2 activity are affected by GTPase function and capsid-CypA interactions.bioRxiv : the preprint server for biology · 2023Article
- Review
- The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Updating on Roles of HIV Intrinsic Factors: A Review of Their Antiviral Mechanisms and Emerging Functions.Intervirology · 2022Review
- Emerging Roles of Cyclophilin A in Regulating Viral Cloaking.Frontiers in microbiology · 2022Review
- HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules.Retrovirology · 2021Review
- Structure, Function, and Interactions of the HIV-1 Capsid Protein.Life (Basel, Switzerland) · 2021Review
- Effect of Different Nuclear Localization Signals on the Subcellular Localization and Anti-HIV-1 Function of the MxB Protein.Frontiers in microbiology · 2021Article
- From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1.Frontiers in microbiology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The type one interferon induced restriction factor Myxovirus resistance B (MxB) restricts HIV-1 nuclear entry evidenced by inhibition of 2-LTR but not linear forms of viral DNA. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. This has suggested that nuclear import mechanism may determine MxB sensitivity. Here we have use genetics to separate HIV-1 nuclear import cofactor dependence from MxB sensitivity. We provide evidence that MxB sensitivity depends on HIV-1 capsid conformation, rather than cofactor recruitment. We show that depleting CPSF6 to change nuclear import pathway does not impact MxB sensitivity, but mutants that recapitulate the effect of Cyclophilin A binding on capsid conformation and dynamics strongly impact MxB sensitivity. We demonstrate that HIV-1 primary isolates have different MxB sensitivities due to cytotoxic T lymphocyte (CTL) selected differences in Gag sequence but similar cofactor dependencies. Overall our work demonstrates a complex relationship between cyclophilin dependence and MxB sensitivity likely driven by CTL escape. We propose that cyclophilin binding provides conformational flexibility to HIV-1 capsid facilitating simultaneous evasion of capsid-targeting restriction factors including TRIM5 as well as MxB.
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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.