HIV-1 capsid is involved in post-nuclear entry steps

@article{Chen2016HIV1CI,
  title={HIV-1 capsid is involved in post-nuclear entry steps},
  author={N. Chen and Lihong Zhou and P. Gane and S. Opp and N. Ball and G. Nicastro and M. Zufferey and Cindy Buffone and J. Luban and D. Selwood and F. Diaz-Griffero and I. Taylor and A. Fassati},
  journal={Retrovirology},
  year={2016},
  volume={13}
}
BackgroundHIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might affect post-nuclear entry steps.ResultsHere we report that C-A1 inhibits HIV-1 integration in a capsid-dependent way. Using molecular docking, we identify an extended binding pocket… Expand
Cone-shaped HIV-1 capsids are transported through intact nuclear pores
TLDR
It is demonstrated that the diameter of the NPC in cellulo is sufficient for the import of apparently intact, coneshaped capsids and detected disrupted and empty capsid fragments, indicating that uncoating of the replication complex occurs by breaking the capsid open, and not by disassembly into individual subunits. Expand
Analysis of CA Content and CPSF6 Dependence of Early HIV-1 Replication Complexes in SupT1-R5 Cells
TLDR
HIV-1 capsids stay largely intact during transport to the nucleus of infected T cells but appear to uncoat upon entry into the nucleoplasm, which supports the hypothesis that capsids protect the HIV-1 genome from cytoplasmic defense mechanisms and target the genome toward the nucleus. Expand
A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing
TLDR
A novel phenotype of capsid stability that has a profound effect on innate sensing of viral DNA by the DNA sensor cGAS is uncovered, suggesting that capsid stabilization improves the shielding of viralDNA from innate sensing. Expand
HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex
TLDR
Two-color stimulated-emission-depletion microscopy indicated that under these circumstances HIV-1 complexes are retained inside the nuclear pore and undergo CA-multimer dependent CPSF6 clustering adjacent to the nuclear basket. Expand
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TLDR
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A DNA-origami nuclear pore mimic reveals nuclear entry mechanisms of HIV-1 capsid
TLDR
DNA-origami mimics of the NPC are used to reveal the mechanistic underpinnings of HIV-1 capsid nuclear entry and find that trimeric interface formed via three capsid protein hexamers is targeted by a triple-arginine (RRR) motif but not the canonical phenylalanine-glycine (FG) motif of NUP153. Expand
HIV-1 uncoating by release of viral cDNA from capsid-like structures in the nucleus of infected cells
TLDR
The data argue for nuclear uncoating by physical disruption rather than cooperative disassembly of the CA-lattice, followed by physical separation from the pre-integration complex. Expand
HIV-1 uncoating by release of viral cDNA from capsid-like structures in the nucleus of infected cells
TLDR
The data argue for nuclear uncoating by physical disruption rather than cooperative disassembly of the CA-lattice, followed by physical separation from the pre-integration complex. Expand
Structure, Function, and Interactions of the HIV-1 Capsid Protein
TLDR
CA displays potential as a therapeutic target for the development of HIV-1 inhibitors through interactions with host cell factors and in the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone. Expand
Visualizing HIV-1 Capsid and Its Interactions with Antivirals and Host Factors
TLDR
Structural insights into the intra- and intermolecular interactions that govern capsid function have enabled development of small molecules, peptides, and truncated proteins to disrupt or stabilize the capsid to inhibit HIV replication. Expand
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