Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration
The HIV/AIDS pandemic is a major global health threat and understanding the detailed molecular mechanisms of HIV replication is critical for the development of novel therapeutics. To replicate, HIV-1 must access the nucleus of infected cells and integrate into host chromosomes, however little is kno...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2011
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| Subjects: |
| _version_ | 1797101263887794176 |
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| author | Zhou, L Sokolskaja, E Jolly, C James, W Cowley, S Fassati, A |
| author_facet | Zhou, L Sokolskaja, E Jolly, C James, W Cowley, S Fassati, A |
| author_sort | Zhou, L |
| collection | OXFORD |
| description | The HIV/AIDS pandemic is a major global health threat and understanding the detailed molecular mechanisms of HIV replication is critical for the development of novel therapeutics. To replicate, HIV-1 must access the nucleus of infected cells and integrate into host chromosomes, however little is known about the events occuring post-nuclear entry but before integration. Hertr we show that the karyopherin Transportin 3 (Tnp3) promotes HIV-1 integration in different cell types. Furthermore Tnp3 binds the viral capsid proteins and tRNAs incorporated into viral particles. Interaction between Tnps, capsid and tRNAs is stronger in the presence of RangGTP, consistent with the possibility that Tnp3 is an export factor for these substrates. In agreement with this interpretation, we found that Tnp3 exports from the nuclei viral tRNAs in a RanGTP-dependent way. Tnp3 also binds and exports from the nuclei some species of cellular tRNAs with a defective 3'CCA end. Depletin of Tnp3 results in a re-distribution of HIV-1 capsid proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic redistribution of capsid proteins. We propose that Tnp3 promotes HIV-1 infection by displacing any capsid and tRNA that remain bound to the pre-integration complex after nuclear entry to facilitate integration. The results also provide evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells. |
| first_indexed | 2024-03-07T05:49:21Z |
| format | Journal article |
| id | oxford-uuid:e854512c-9c13-4cd5-b8ca-89ed69ae5512 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:49:21Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:e854512c-9c13-4cd5-b8ca-89ed69ae55122022-03-27T10:45:47ZTransportin 3 promotes a nuclear maturation step required for efficient HIV-1 integrationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e854512c-9c13-4cd5-b8ca-89ed69ae5512HIV/AIDSPathologyEnglishOxford University Research Archive - ValetPublic Library of Science2011Zhou, LSokolskaja, EJolly, CJames, WCowley, SFassati, AThe HIV/AIDS pandemic is a major global health threat and understanding the detailed molecular mechanisms of HIV replication is critical for the development of novel therapeutics. To replicate, HIV-1 must access the nucleus of infected cells and integrate into host chromosomes, however little is known about the events occuring post-nuclear entry but before integration. Hertr we show that the karyopherin Transportin 3 (Tnp3) promotes HIV-1 integration in different cell types. Furthermore Tnp3 binds the viral capsid proteins and tRNAs incorporated into viral particles. Interaction between Tnps, capsid and tRNAs is stronger in the presence of RangGTP, consistent with the possibility that Tnp3 is an export factor for these substrates. In agreement with this interpretation, we found that Tnp3 exports from the nuclei viral tRNAs in a RanGTP-dependent way. Tnp3 also binds and exports from the nuclei some species of cellular tRNAs with a defective 3'CCA end. Depletin of Tnp3 results in a re-distribution of HIV-1 capsid proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic redistribution of capsid proteins. We propose that Tnp3 promotes HIV-1 infection by displacing any capsid and tRNA that remain bound to the pre-integration complex after nuclear entry to facilitate integration. The results also provide evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells. |
| spellingShingle | HIV/AIDS Pathology Zhou, L Sokolskaja, E Jolly, C James, W Cowley, S Fassati, A Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration |
| title | Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration |
| title_full | Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration |
| title_fullStr | Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration |
| title_full_unstemmed | Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration |
| title_short | Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration |
| title_sort | transportin 3 promotes a nuclear maturation step required for efficient hiv 1 integration |
| topic | HIV/AIDS Pathology |
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