1. Cell Biology
  2. Microbiology and Infectious Disease
Download icon

Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2

  1. Melissa Kane
  2. Stephanie V Rebensburg
  3. Matthew A Takata
  4. Trinity M Zang
  5. Masahiro Yamashita
  6. Mamuka Kvaratskhelia
  7. Paul D Bieniasz  Is a corresponding author
  1. Rockefeller University, United States
  2. University of Colorado Denver, United States
  3. Aaron Diamond AIDS Research Center, United States
Research Article
  • Cited 8
  • Views 1,948
  • Annotations
Cite this article as: eLife 2018;7:e35738 doi: 10.7554/eLife.35738

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.

Article and author information

Author details

  1. Melissa Kane

    Laboratory of Retrovirology, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Stephanie V Rebensburg

    Division of Infectious Diseases, University of Colorado Denver, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew A Takata

    Laboratory of Retrovirology, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Trinity M Zang

    Laboratory of Retrovirology, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Masahiro Yamashita

    Aaron Diamond AIDS Research Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Mamuka Kvaratskhelia

    Division of Infectious Diseases, University of Colorado Denver, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Paul D Bieniasz

    Laboratory of Retrovirology, Rockefeller University, New York, United States
    For correspondence
    pbieniasz@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2368-3719

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

  1. Viviana Simon, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: February 8, 2018
  2. Accepted: August 6, 2018
  3. Accepted Manuscript published: August 7, 2018 (version 1)
  4. 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.

Metrics

  • 1,948
    Page views
  • 409
    Downloads
  • 8
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)