HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the Nuclear Pore Complex
- University of Heidelberg, Germany
- Cited 30
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Abstract
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.
Article and author information
Author details
Hans-Georg Kräusslich
Funding
Deutsche Forschungsgemeinschaft (SFB1129)
- Barbara Müller
- Hans-Georg Kräusslich
Deutsches Zentrum für Infektionsforschung (TTU HIV)
- Hans-Georg Kräusslich
Deutsche Forschungsgemeinschaft (SPP1923)
- Hans-Georg Kräusslich
Heidelberg Biosciences International Graduate School
- David Alejandro Bejarano
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wesley I Sundquist, University of Utah School of Medicine, United States
Publication history
- Received: September 7, 2018
- Accepted: January 16, 2019
- Accepted Manuscript published: January 23, 2019 (version 1)
- Version of Record published: March 5, 2019 (version 2)
Copyright
© 2019, Bejarano et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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