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...

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Autores principales:	Lihong Zhou, Elena Sokolskaja, Clare Jolly, William James, Sally A Cowley, Ariberto Fassati
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f9114f3b0cf94e9abe5cf249eb3eb68a
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spelling	oai:doaj.org-article:f9114f3b0cf94e9abe5cf249eb3eb68a2021-11-18T06:03:05ZTransportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration.1553-73661553-737410.1371/journal.ppat.1002194https://doaj.org/article/f9114f3b0cf94e9abe5cf249eb3eb68a2011-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21901095/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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 occurring post-nuclear entry but before integration. Here 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 Tnp3, capsid and tRNAs is stronger in the presence of RanGTP, 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. Depletion 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.Lihong ZhouElena SokolskajaClare JollyWilliam JamesSally A CowleyAriberto FassatiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 8, p e1002194 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Lihong Zhou Elena Sokolskaja Clare Jolly William James Sally A Cowley Ariberto Fassati Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration.
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 occurring post-nuclear entry but before integration. Here 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 Tnp3, capsid and tRNAs is stronger in the presence of RanGTP, 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. Depletion 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.
format	article
author	Lihong Zhou Elena Sokolskaja Clare Jolly William James Sally A Cowley Ariberto Fassati
author_facet	Lihong Zhou Elena Sokolskaja Clare Jolly William James Sally A Cowley Ariberto Fassati
author_sort	Lihong Zhou
title	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_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_sort	transportin 3 promotes a nuclear maturation step required for efficient hiv-1 integration.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f9114f3b0cf94e9abe5cf249eb3eb68a
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Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration.

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