IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33662-6.html
   My bibliography  Save this article

Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection

Author

Listed:
  • Guochao Wei

    (University of Colorado School of Medicine)

  • Naseer Iqbal

    (University of Colorado School of Medicine)

  • Valentine V. Courouble

    (The Scripps Research Institute)

  • Ashwanth C. Francis

    (Florida State University
    Emory University)

  • Parmit K. Singh

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Arpa Hudait

    (The University of Chicago)

  • Arun S. Annamalai

    (University of Colorado School of Medicine)

  • Stephanie Bester

    (University of Colorado School of Medicine)

  • Szu-Wei Huang

    (University of Colorado School of Medicine
    National Cancer Institute)

  • Nikoloz Shkriabai

    (University of Colorado School of Medicine)

  • Lorenzo Briganti

    (University of Colorado School of Medicine)

  • Reed Haney

    (University of Colorado School of Medicine)

  • Vineet N. KewalRamani

    (National Cancer Institute)

  • Gregory A. Voth

    (The University of Chicago)

  • Alan N. Engelman

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Gregory B. Melikyan

    (Emory University)

  • Patrick R. Griffin

    (The Scripps Research Institute)

  • Francisco Asturias

    (University of Colorado School of Medicine)

  • Mamuka Kvaratskhelia

    (University of Colorado School of Medicine)

Abstract

Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short phenylalanine-glycine (FG) containing peptides with isolated capsid hexamers have been characterized, how these cellular factors functionally engage with biologically relevant mature HIV-1 capsid lattices is unknown. Here we show that prion-like low complexity regions (LCRs) enable avid CPSF6, NUP153 and SEC24C binding to capsid lattices. Structural studies revealed that multivalent CPSF6 assembly is mediated by LCR-LCR interactions, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. In infected cells, avid CPSF6 LCR-mediated binding to HIV-1 cores is essential for functional virus-host interactions. The investigational drug lenacapavir accesses unoccupied hydrophobic pockets in the complex to potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results establish previously undescribed mechanisms of virus-host interactions and antiviral action.

Suggested Citation

  • Guochao Wei & Naseer Iqbal & Valentine V. Courouble & Ashwanth C. Francis & Parmit K. Singh & Arpa Hudait & Arun S. Annamalai & Stephanie Bester & Szu-Wei Huang & Nikoloz Shkriabai & Lorenzo Briganti , 2022. "Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33662-6
    DOI: 10.1038/s41467-022-33662-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33662-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33662-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. John O. Link & Martin S. Rhee & Winston C. Tse & Jim Zheng & John R. Somoza & William Rowe & Rebecca Begley & Anna Chiu & Andrew Mulato & Derek Hansen & Eric Singer & Luong K. Tsai & Rujuta A. Bam & C, 2020. "Clinical targeting of HIV capsid protein with a long-acting small molecule," Nature, Nature, vol. 584(7822), pages 614-618, August.
    2. Gongpu Zhao & Juan R. Perilla & Ernest L. Yufenyuy & Xin Meng & Bo Chen & Jiying Ning & Jinwoo Ahn & Angela M. Gronenborn & Klaus Schulten & Christopher Aiken & Peijun Zhang, 2013. "Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics," Nature, Nature, vol. 497(7451), pages 643-646, May.
    3. Ashwanth C. Francis & Mariana Marin & Parmit K. Singh & Vasudevan Achuthan & Mathew J. Prellberg & Kristina Palermino-Rowland & Shuiyun Lan & Philip R. Tedbury & Stefan G. Sarafianos & Alan N. Engelma, 2020. "HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guangai Xue & Hyun Jae Yu & Cindy Buffone & Szu-Wei Huang & KyeongEun Lee & Shih Lin Goh & Anna T. Gres & Mehmet Hakan Guney & Stefan G. Sarafianos & Jeremy Luban & Felipe Diaz-Griffero & Vineet N. Ke, 2023. "The HIV-1 capsid core is an opportunistic nuclear import receptor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiaojun Wei & Xiaoqin Wang & Zehui Zhang & Yuanyuan Luo & Zixin Wang & Wen Xiong & Piyush K. Jain & John R. Monnier & Hui Wang & Tony Y. Hu & Chuanbing Tang & Helmut Albrecht & Chang Liu, 2022. "A click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Jordy Homing Lam & Aiichiro Nakano & Vsevolod Katritch, 2024. "Scalable computation of anisotropic vibrations for large macromolecular assemblies," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Anna T. Gres & Karen A. Kirby & William M. McFadden & Haijuan Du & Dandan Liu & Chaoyi Xu & Alexander J. Bryer & Juan R. Perilla & Jiong Shi & Christopher Aiken & Xiaofeng Fu & Peijun Zhang & Ashwanth, 2023. "Multidisciplinary studies with mutated HIV-1 capsid proteins reveal structural mechanisms of lattice stabilization," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Guangai Xue & Hyun Jae Yu & Cindy Buffone & Szu-Wei Huang & KyeongEun Lee & Shih Lin Goh & Anna T. Gres & Mehmet Hakan Guney & Stefan G. Sarafianos & Jeremy Luban & Felipe Diaz-Griffero & Vineet N. Ke, 2023. "The HIV-1 capsid core is an opportunistic nuclear import receptor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Adel Al Jord & Gaëlle Letort & Soline Chanet & Feng-Ching Tsai & Christophe Antoniewski & Adrien Eichmuller & Christelle Da Silva & Jean-René Huynh & Nir S. Gov & Raphaël Voituriez & Marie-Émilie Terr, 2022. "Cytoplasmic forces functionally reorganize nuclear condensates in oocytes," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Guido Schryen & Natalia Kliewer & Andreas Fink, 2020. "High Performance Business Computing," Business & Information Systems Engineering: The International Journal of WIRTSCHAFTSINFORMATIK, Springer;Gesellschaft für Informatik e.V. (GI), vol. 62(1), pages 1-3, February.
    7. Yuta Sawanaka & Masahiro Yamashina & Hiroyoshi Ohtsu & Shinji Toyota, 2022. "A self-complementary macrocycle by a dual interaction system," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33662-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.