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HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex

Nuclear entry of HIV-1 replication complexes through intact nuclear pore complexes is critical for successful infection. The host protein cleavage-and-polyadenylation-specificity-factor-6 (CPSF6) has been implicated in different stages of early HIV-1 replication. Applying quantitative microscopy of...

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Main Authors: Bejarano Acuña, David Alejandro (Author) , Peng, Ke (Author) , Laketa, Vibor (Author) , Börner, Kathleen (Author) , Jost, Katharina Laurence (Author) , Lucic, Bojana (Author) , Lusic, Marina (Author) , Müller, Barbara (Author) , Kräusslich, Hans-Georg (Author)
Format: Article (Journal)
Language:English
Published: 23 January 2019
In: eLife
Year: 2019, Volume: 8
ISSN:2050-084X
DOI:10.7554/eLife.41800
Online Access:Verlag, Volltext: https://doi.org/10.7554/eLife.41800
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Author Notes:David Alejandro Bejarano, Ke Peng, Vibor Laketa, Kathleen Börner, K. Laurence Jost, Bojana Lucic, Bärbel Glass, Marina Lusic, Barbara Müller, Hans-Georg Kräusslich
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Summary:Nuclear entry of HIV-1 replication complexes through intact nuclear pore complexes is critical for successful infection. The host protein cleavage-and-polyadenylation-specificity-factor-6 (CPSF6) has been implicated in different stages of early HIV-1 replication. Applying quantitative microscopy of HIV-1 reverse-transcription and pre-integration-complexes (RTC/PIC), we show that CPSF6 is strongly recruited to nuclear replication complexes but absent from cytoplasmic RTC/PIC in primary human macrophages. Depletion of CPSF6 or lack of CPSF6 binding led to accumulation of HIV-1 subviral complexes at the nuclear envelope of macrophages and reduced infectivity. Two-color stimulated-emission-depletion microscopy indicated that under these circumstances HIV-1 complexes are retained inside the nuclear pore and undergo CA-multimer dependent CPSF6 clustering adjacent to the nuclear basket. We propose that nuclear entry of HIV-1 subviral complexes in macrophages is mediated by consecutive binding of Nup153 and CPSF6 to the hexameric CA lattice.
Item Description:Gesehen am 11.07.2019
Physical Description:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.41800

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