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Flexible Use of Nuclear Import Pathways by HIV-1

  1. Author:
    Lee, K.
    Ambrose, Z.
    Martin, T. D.
    Oztop, I.
    Mulky, A.
    Julias, J. G.
    Vandegraaff, N.
    Baumann, J. G.
    Wang, R.
    Yuen, W.
    Takemura, T.
    Shelton, K.
    Taniuchi, I.
    Li, Y.
    Sodroski, J.
    Littman, D. R.
    Coffin, J. M.
    Hughes, S. H.
    Unutmaz, D.
    Engelman, A.
    KewalRamani, V. N.
  2. Author Address

    [Lee, KyeongEun; Ambrose, Zandrea; Martin, Thomas D.; Mulky, Alok; Baumann, Joerg G.; Yuen, Wendy; Takemura, Taichiro; Shelton, Kenneth; Hughes, Stephen H.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Oztop, Ilker; Vandegraaff, Nick; Li, Yuan; Sodroski, Joseph; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Julias, John G.] SAIC Frederick, Frederick, MD 21702 USA. [Wang, Rui; Unutmaz, Derya] NYU, Sch Med, Dept Pathol & Microbiol, New York, NY 10016 USA. [Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Littman, Dan R.] NYU, Sch Med, Mol Pathogenesis Program, Skirball Inst Biomol Med, New York, NY 10016 USA. [Taniuchi, Ichiro] Riken Res Ctr Allergy & Immunol, Lab Transcript Regulat, Yokohama, Kanagawa 2300045, Japan. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Sackler Sch Biomed Sci, Boston, MA 02111 USA.;KewalRamani, VN, NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.;vineet@mail.nih.gov
    1. Year: 2010
    2. Date: Mar
  1. Journal: Cell Host & Microbe
    1. 7
    2. 3
    3. Pages: 221-233
  2. Type of Article: Article
  3. ISSN: 1931-3128
  1. Abstract:

    HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the retroviral preintegration complex (PIG), into the nucleus. Too large for passive diffusion through nuclear pore complexes (NPCs), PICs use cellular nuclear transport mechanisms and nucleoporins (NUPs), the NPC components that permit selective nuclear-cytoplasmic exchange, but the details remain unclear. Here we identify a fragment of the cleavage and polyadenylation factor 6, CPSF6, as a potent inhibitor of HIV-1 infection. When enriched in the cytoplasm, CPSF6 prevents HIV-1 nuclear entry by targeting the viral capsid (CA). HIV-1 harboring the N74D mutation in CA fails to interact with CPSF6 and evades the nuclear import restriction. Interestingly, whereas wild-type HIV-1 requires NUP153, N74D HIV-1 mimics feline immunodeficiency virus nuclear import requirements and is more sensitive to NUP155 depletion. These findings reveal a remarkable flexibility in HIV-1 nuclear transport and highlight a single residue in CA as essential in regulating interactions with NUPs.

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External Sources

  1. DOI: 10.1016/j.chom.2010.02.007
  2. WOS: 000275947500007

Library Notes

  1. Fiscal Year: FY2009-2010
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