Cone-shaped HIV-1 capsids are transported through intact nuclear pores

Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid...

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Hauptverfasser: Zila, Vojtech (VerfasserIn) , Margiotta, Erica (VerfasserIn) , Turoňová, Beata (VerfasserIn) , Müller, Thorsten G. (VerfasserIn) , Zimmerli, Christian Eugen (VerfasserIn) , Mattei, Simone (VerfasserIn) , Allegretti, Matteo (VerfasserIn) , Börner, Kathleen (VerfasserIn) , Rada, Jona (VerfasserIn) , Müller, Barbara (VerfasserIn) , Lusic, Marina (VerfasserIn) , Kräusslich, Hans-Georg (VerfasserIn) , Beck, Martin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 10 February 2021
In: Cell
Year: 2021, Jahrgang: 184, Heft: 4, Pages: 1032-1046, e1-e18
ISSN:1097-4172
DOI:10.1016/j.cell.2021.01.025
Online-Zugang:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2021.01.025
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867421000684
Volltext
Verfasserangaben:Vojtech Zila, Erica Margiotta, Beata Turoňová, Thorsten G. Müller, Christian E. Zimmerli, Simone Mattei, Matteo Allegretti, Kathleen Börner, Jona Rada, Barbara Müller, Marina Lusic, Hans-Georg Kräusslich, Martin Beck

MARC

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520 |a Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid uncoating has to occur prior to nuclear import. Here, we combined correlative light and electron microscopy with subtomogram averaging to capture the structural status of reverse transcription-competent HIV-1 complexes in infected T cells. We demonstrated that the diameter of the NPC in cellulo is sufficient for the import of apparently intact, cone-shaped capsids. Subsequent to nuclear import, we 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. Our data directly visualize a key step in HIV-1 replication and enhance our mechanistic understanding of the viral life cycle. 
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