Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2
Abstract
HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between the capsid protein (CA) and nucleoporins (Nups). Here, we show that HIV-1 CA can bind multiple Nups, and that both natural and manipulated variation in Nup levels impacts HIV-1 infection in a manner that is strikingly dependent on cell-type, cell-cycle, and cyclophilin A (CypA). We also show that Nups mediate the function of the antiviral protein MX2, and that MX2 can variably inhibit non-viral NLS function. Remarkably, both enhancing and inhibiting effects of cyclophilin A and MX2 on various HIV-1 CA mutants could be induced or abolished by manipulating levels of the Nup93 subcomplex, the Nup62 subcomplex, NUP88, NUP21, RANBP2, or NUP153. Our findings suggest that several Nup-dependent 'pathways' are variably exploited by HIV-1 to target host DNA in a cell-type, cell-cycle, CypA and CA-sequence dependent manner, and are differentially inhibited by MX2.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Howard Hughes Medical Institute (Investigator Award)
- Paul D Bieniasz
National Institute of Allergy and Infectious Diseases (R3764003)
- Paul D Bieniasz
National Institute of Allergy and Infectious Diseases (R01AI100720)
- Masahiro Yamashita
National Institute of Allergy and Infectious Diseases (R01AI062520)
- Mamuka Kvaratskhelia
National Institute of Allergy and Infectious Diseases (F32AI116263)
- Melissa Kane
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Viviana Simon, Icahn School of Medicine at Mount Sinai, United States
Version history
- Received: February 8, 2018
- Accepted: August 6, 2018
- Accepted Manuscript published: August 7, 2018 (version 1)
- Version of Record published: August 20, 2018 (version 2)
Copyright
© 2018, Kane 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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