Title |
HIV-1 capsid is involved in post-nuclear entry steps
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Published in |
Retrovirology, April 2016
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DOI | 10.1186/s12977-016-0262-0 |
Pubmed ID | |
Authors |
Nan-Yu Chen, Lihong Zhou, Paul J. Gane, Silvana Opp, Neil J. Ball, Giuseppe Nicastro, Madeleine Zufferey, Cindy Buffone, Jeremy Luban, David Selwood, Felipe Diaz-Griffero, Ian Taylor, Ariberto Fassati |
Abstract |
HIV-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. Here we report that C-A1 inhibits HIV-1 integration in a capsid-dependent way. Using molecular docking, we identify an extended binding pocket delimited by two adjacent capsid monomers where C-A1 is predicted to bind. Isothermal titration calorimetry confirmed that C-A1 binds to hexameric capsid. Cyclosporine washout assays in Jurkat CD4+ T cells expressing engineered human TRIMCyp showed that C-A1 causes faster and greater escape from TRIMCyp restriction. Sub-cellular fractionation showed that small amounts of capsid accumulated in the nuclei of infected cells and C-A1 reduced the nuclear capsid. A105S and N74D capsid mutant viruses did not accumulate capsid in the nucleus, irrespective of C-A1 treatment. Depletion of Nup153, a nucleoporin located at the nuclear side of the nuclear pore that binds to HIV-1 capsid, made the virus less susceptible to TRIMCyp restriction, suggesting that Nup153 may help maintain some integrity of the viral core in the nucleus. Furthermore C-A1 increased binding of CPSF6, a nuclear protein, to capsid. Our results indicate that capsid is involved in post-nuclear entry steps preceding integration. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 68 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 19 | 28% |
Researcher | 14 | 21% |
Student > Master | 6 | 9% |
Student > Doctoral Student | 3 | 4% |
Student > Bachelor | 3 | 4% |
Other | 9 | 13% |
Unknown | 14 | 21% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 20 | 29% |
Immunology and Microbiology | 12 | 18% |
Agricultural and Biological Sciences | 10 | 15% |
Chemistry | 3 | 4% |
Medicine and Dentistry | 3 | 4% |
Other | 4 | 6% |
Unknown | 16 | 24% |