4.6 Review

Nuclear Import of HIV-1

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Summary: The study reveals that the diameter of the nuclear pore complex in infected T cells is sufficient for the import of intact, cone-shaped capsids, with uncoating occurring by breaking the capsid open after nuclear import rather than disassembly into individual subunits. This visualization of a key step in HIV-1 replication enhances our understanding of the viral life cycle.
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Summary: The study showed that HIV-1 cores maintain their integrity until just before integration, losing a content marker approximately 1 to 3 minutes before uncoating. This suggests that viral cores retain their integrity and remain separated from the nuclear environment before uncoating occurs.

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Summary: The capsid (CA) protein of HIV-1 plays crucial roles in shielding the reverse transcription complex, facilitating trafficking to the nucleus, and forming the capsid core during viral maturation. Understanding the functions of CA could lead to the development of potential therapeutic targets for HIV-1 inhibitors.

LIFE-BASEL (2021)

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Summary: Our study reveals an interaction between CPSF6 and CypA that is crucial for cytoplasmic capsid trafficking and HIV-1 infection. CypA plays a role in preventing premature engagement of HIV-1 capsid with cytoplasmic CPSF6, potentially explaining variations in capsid trafficking and uncoating in different cell types. Understanding these processes can lead to the development of better drugs for preventing HIV infection and pathogenesis.
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HIV-1 uncoating by release of viral cDNA from capsid-like structures in the nucleus of infected cells

Thorsten G. Mueller et al.

Summary: The study found that uncoating of HIV-1 occurs through physical disruption in the cell nucleus rather than cooperative disassembly of the CA-lattice, followed by physical separation from the pre-integration complex.
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HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration

Anabel Guedan et al.

Summary: The stability of the HIV-1 core is crucial for infection, and introducing cysteine residues into CA lattice can increase stability. Hyper-stable mutants with reduced uncoating ability were found to enter the nucleus and complete reverse transcription, suggesting the importance of capsid lattice flexibility for successful integration.

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HIV-1 uncoats in the nucleus near sites of integration

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HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains

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Cyclophilin A protects HIV-1 from restriction by human TRIM5α

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Martin Beck et al.

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Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection

Adarsh Dharan et al.

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Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNA Export Platform

Javier Fernandez-Martinez et al.

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Simple rules for passive diffusion through the nuclear pore complex

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SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV

Daniel A. Donahue et al.

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HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis

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A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin

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Time-Resolved Imaging of Single HIV-1 Uncoating In Vitro and in Living Cells

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Microtubule-associated Proteins 1 (MAP1) Promote Human Immunodeficiency Virus Type I (HIV-1) Intracytoplasmic Routing to the Nucleus

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Atomic-level modelling of the HIV capsid

Owen Pornillos et al.

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Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription

Amy E. Hulme et al.

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Interplay between HIV Entry and Transportin-SR2 Dependency

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The Nuclear Pore Complex Has Entered the Atomic Age

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Natively unfolded nucleoporins gate protein diffusion across the nuclear pore complex

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Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor

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