HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72693
Title:
HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore.
Authors:
Arhel, Nathalie J; Souquere-Besse, Sylvie; Munier, Sandie; Souque, Philippe; Guadagnini, Stéphanie; Rutherford, Sandra A; Prévost, Marie-Christine; Allen, Terence D; Charneau, Pierre
Abstract:
The HIV-1 central DNA Flap acts as a cis-acting determinant of HIV-1 genome nuclear import. Indeed, DNA-Flap re-insertion within lentiviral-derived gene transfer vectors strongly stimulates gene transfer efficiencies. In this study, we sought to understand the mechanisms by which the central DNA Flap mediates HIV-1 nuclear import. Here, we show that reverse transcription (RT degrees) occurs within an intact capsid (CA) shell, independently of the routing process towards the nuclear membrane, and that uncoating is not an immediate post-fusion event, but rather occurs at the nuclear pore upon RT degrees completion. We provide the first observation with ultrastructural resolution of intact intracellular HIV-1 CA shells by scanning electron microscopy. In the absence of central DNA Flap formation, uncoating is impaired and linear DNA remains trapped within an integral CA shell precluding translocation through the nuclear pore. These data show that DNA Flap formation, the very last event of HIV-1 RT degrees, acts as a viral promoting element for the uncoating of HIV-1 at the nuclear pore.
Affiliation:
Groupe de Virologie Moléculaire et Vectorologie, CNRS-URA 3015, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Citation:
HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore. 2007, 26 (12):3025-37 EMBO J.
Journal:
The EMBO Journal
Issue Date:
20-Jun-2007
URI:
http://hdl.handle.net/10541/72693
DOI:
10.1038/sj.emboj.7601740
PubMed ID:
17557080
Type:
Article
Language:
en
ISSN:
0261-4189
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorArhel, Nathalie J-
dc.contributor.authorSouquere-Besse, Sylvie-
dc.contributor.authorMunier, Sandie-
dc.contributor.authorSouque, Philippe-
dc.contributor.authorGuadagnini, Stéphanie-
dc.contributor.authorRutherford, Sandra A-
dc.contributor.authorPrévost, Marie-Christine-
dc.contributor.authorAllen, Terence D-
dc.contributor.authorCharneau, Pierre-
dc.date.accessioned2009-07-07T09:31:33Z-
dc.date.available2009-07-07T09:31:33Z-
dc.date.issued2007-06-20-
dc.identifier.citationHIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore. 2007, 26 (12):3025-37 EMBO J.en
dc.identifier.issn0261-4189-
dc.identifier.pmid17557080-
dc.identifier.doi10.1038/sj.emboj.7601740-
dc.identifier.urihttp://hdl.handle.net/10541/72693-
dc.description.abstractThe HIV-1 central DNA Flap acts as a cis-acting determinant of HIV-1 genome nuclear import. Indeed, DNA-Flap re-insertion within lentiviral-derived gene transfer vectors strongly stimulates gene transfer efficiencies. In this study, we sought to understand the mechanisms by which the central DNA Flap mediates HIV-1 nuclear import. Here, we show that reverse transcription (RT degrees) occurs within an intact capsid (CA) shell, independently of the routing process towards the nuclear membrane, and that uncoating is not an immediate post-fusion event, but rather occurs at the nuclear pore upon RT degrees completion. We provide the first observation with ultrastructural resolution of intact intracellular HIV-1 CA shells by scanning electron microscopy. In the absence of central DNA Flap formation, uncoating is impaired and linear DNA remains trapped within an integral CA shell precluding translocation through the nuclear pore. These data show that DNA Flap formation, the very last event of HIV-1 RT degrees, acts as a viral promoting element for the uncoating of HIV-1 at the nuclear pore.en
dc.language.isoenen
dc.subject.meshBase Sequence-
dc.subject.meshBlotting, Southern-
dc.subject.meshDNA Primers-
dc.subject.meshDNA, Viral-
dc.subject.meshHIV-1-
dc.subject.meshMicroscopy, Confocal-
dc.subject.meshMicroscopy, Electron, Scanning-
dc.subject.meshNuclear Pore-
dc.subject.meshTranscription, Genetic-
dc.subject.meshViral Proteins-
dc.subject.meshVirus Integration-
dc.titleHIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore.en
dc.typeArticleen
dc.contributor.departmentGroupe de Virologie Moléculaire et Vectorologie, CNRS-URA 3015, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.en
dc.identifier.journalThe EMBO Journalen

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