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Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration

  1. Author:
    Achuthan, Vasudevan
    Perreira, Jill M
    Sowd, Gregory A
    Puray-Chavez, Maritza
    McDougall, William M
    Paulucci-Holthauzen, Adriana
    Wu, Xiaolin
    Fadel, Hind J
    Poeschla, Eric M
    Multani, Asha S
    Hughes, Stephen
    Sarafianos, Stefan G
    Brass, Abraham L
    Engelman, Alan N

  2. Author Address

    Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA., Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA., Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Leidos Biomedical Research, Inc., Frederick, MD 21702, USA., Division of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA., Division of Infectious Diseases, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA., HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA; Gastroenterology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: abraham.brass@umassmed.edu., Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: alan_engelman@dfci.harvard.edu.,
    1. Year: 2018
    2. Date: Sep 12
    3. Epub Date: 2018 08 24
  2. Journal: Cell host & microbe
    1. 24
    2. 3
    3. Pages: 392-404.e8
  4. Type of Article: Article
  5. ISSN: 1931-3128
  1. Abstract:

    HIV-1 integration into the host genome favors actively transcribed genes. Prior work indicated that the nuclear periphery provides the architectural basis for integration site selection, with viral capsid-binding host cofactor CPSF6 and viral integrase-binding cofactor LEDGF/p75 contributing to selection of individual sites. Here, by investigating the early phase of infection, we determine that HIV-1 traffics throughout the nucleus for integration. CPSF6-capsid interactions allow the virus to bypass peripheral heterochromatin and penetrate the nuclear structure for integration. Loss of interaction with CPSF6 dramatically alters virus localization toward the nuclear periphery and integration into transcriptionally repressed lamina-associated heterochromatin, while loss of LEDGF/p75 does not significantly affect intranuclear HIV-1 localization. Thus, CPSF6 serves as a master regulator of HIV-1 intranuclear localization by trafficking viral preintegration complexes away from heterochromatin at the periphery toward gene-dense chromosomal regions within the nuclear interior. Copyright © 2018 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.chom.2018.08.002
  3. PMID: 30173955
  4. View record in Web of Science®
  5. WOS: 000446887200011
  6. PII : S1931-3128(18)30430-X

Library Notes

  1. Fiscal Year: FY2017-2018
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