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Pan-retroviral Nucleocapsid-Mediated Phase Separation Regulates Genomic RNA Positioning and Trafficking

  1. Author:
    Monette, Anne
    Niu, Meijuan
    Chen, Lois
    Rao, Shringar
    Gorelick,Robert
    Mouland, Andrew John

  2. Author Address

    HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr 233;al, QC H3T 1E2, Canada. Electronic address: anne.monette@mail.mcgill.ca., HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr 233;al, QC H3T 1E2, Canada; Department of Microbiology and Immunology, McGill University, Montr 233;al, QC H3A 2B4, Canada., HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr 233;al, QC H3T 1E2, Canada; Department of Biochemistry, Erasmus University Medical Center, Ee634, PO Box 2040, 3000CA Rotterdam, the Netherlands., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr 233;al, QC H3T 1E2, Canada; Department of Microbiology and Immunology, McGill University, Montr 233;al, QC H3A 2B4, Canada; Department of Medicine, McGill University, Montr 233;al, QC H3G 2M1, Canada. Electronic address: andrew.mouland@mcgill.ca.,
    1. Year: 2020
    2. Date: Apr 21
  2. Journal: Cell reports
    1. 31
    2. 3
    3. Pages: 107520
  4. Type of Article: Article
  5. Article Number: 107520
  6. ISSN: 2211-1247
  1. Abstract:

    The duality of liquid-liquid phase separation (LLPS) of cellular components into membraneless organelles defines the nucleation of both normal and disease processes including stress granule (SG) assembly. From mounting evidence of LLPS utility by viruses, we discover that HIV-1 nucleocapsid (NC) protein condenses into zinc-finger (ZnF)-dependent LLPSs that are dynamically influenced by cytosolic factors. ZnF-dependent and Zinc (Zn2+)-chelation-sensitive NC-LLPS are formed in live cells. NC-Zn2+ ejection reverses the HIV-1 blockade on SG assembly, inhibits NC-SG assembly, disrupts NC/Gag-genomic RNA (vRNA) ribonucleoprotein complexes, and causes nuclear sequestration of NC and the vRNA, inhibiting Gag expression and virus release. NC ZnF mutagenesis eliminates the HIV-1 blockade of SG assembly and repositions vRNA to SGs. We find that NC-mediated, Zn2+-coordinated phase separation is conserved among diverse retrovirus subfamilies, illustrating that this exquisitely evolved Zn2+-dependent feature of virus replication represents a critical target for pan-antiretroviral therapies. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2020.03.084
  3. PMID: 32320662
  4. View record in Web of Science®
  5. WOS: 000526939900016
  6. PII : S2211-1247(20)30419-8

Library Notes

  1. Fiscal Year: FY2019-2020
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