Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2
- Rockefeller University, United States
- University of Colorado Denver, United States
- Aaron Diamond AIDS Research Center, United States
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.
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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.
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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Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2
eLife 7:e35738.
https://doi.org/10.7554/eLife.35738
