IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40227-8.html
   My bibliography  Save this article

HIV-1-induced nuclear invaginations mediated by VAP-A, ORP3, and Rab7 complex explain infection of activated T cells

Author

Listed:
  • Mark F. Santos

    (Touro University Nevada College of Osteopathic Medicine)

  • Germana Rappa

    (Touro University Nevada College of Osteopathic Medicine)

  • Jana Karbanová

    (Technische Universität Dresden)

  • Patrizia Diana

    (University of Palermo)

  • Girolamo Cirrincione

    (University of Palermo)

  • Daniela Carbone

    (University of Palermo)

  • David Manna

    (Touro College of Osteopathic Medicine, Middletown)

  • Feryal Aalam

    (Touro University Nevada College of Osteopathic Medicine)

  • David Wang

    (Touro University Nevada College of Osteopathic Medicine)

  • Cheryl Vanier

    (Touro University Nevada College of Osteopathic Medicine
    Imgen Research, LLC)

  • Denis Corbeil

    (Technische Universität Dresden)

  • Aurelio Lorico

    (Touro University Nevada College of Osteopathic Medicine)

Abstract

The mechanism of human immunodeficiency virus 1 (HIV-1) nuclear entry, required for productive infection, is not fully understood. Here, we report that in HeLa cells and activated CD4+ T cells infected with HIV-1 pseudotyped with VSV-G and native Env protein, respectively, Rab7+ late endosomes containing endocytosed HIV-1 promote the formation of nuclear envelope invaginations (NEIs) by a molecular mechanism involving the VOR complex, composed of the outer nuclear membrane protein VAP-A, hyperphosphorylated ORP3 and Rab7. Silencing VAP-A or ORP3 and drug-mediated impairment of Rab7 binding to ORP3-VAP-A inhibited the nuclear transfer of the HIV-1 components and productive infection. In HIV-1-resistant quiescent CD4+ T cells, ORP3 was not hyperphosphorylated and neither VOR complex nor NEIs were formed. This new cellular pathway and its molecular players are potential therapeutic targets, perhaps shared by other viruses that require nuclear entry to complete their life cycle.

Suggested Citation

  • Mark F. Santos & Germana Rappa & Jana Karbanová & Patrizia Diana & Girolamo Cirrincione & Daniela Carbone & David Manna & Feryal Aalam & David Wang & Cheryl Vanier & Denis Corbeil & Aurelio Lorico, 2023. "HIV-1-induced nuclear invaginations mediated by VAP-A, ORP3, and Rab7 complex explain infection of activated T cells," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40227-8
    DOI: 10.1038/s41467-023-40227-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40227-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40227-8?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. Alexander von Appen & Jan Kosinski & Lenore Sparks & Alessandro Ori & Amanda L. DiGuilio & Benjamin Vollmer & Marie-Therese Mackmull & Niccolo Banterle & Luca Parca & Panagiotis Kastritis & Katarzyna , 2015. "In situ structural analysis of the human nuclear pore complex," Nature, Nature, vol. 526(7571), pages 140-143, October.
    Full references (including those not matched with items on IDEAS)

    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. Vincent Louvel & Romuald Haase & Olivier Mercey & Marine H. Laporte & Thibaut Eloy & Étienne Baudrier & Denis Fortun & Dominique Soldati-Favre & Virginie Hamel & Paul Guichard, 2023. "iU-ExM: nanoscopy of organelles and tissues with iterative ultrastructure expansion microscopy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Michael P Lake & Louis-S Bouchard, 2017. "Targeted nanodiamonds for identification of subcellular protein assemblies in mammalian cells," PLOS ONE, Public Library of Science, vol. 12(6), pages 1-18, June.
    3. David Winogradoff & Han-Yi Chou & Christopher Maffeo & Aleksei Aksimentiev, 2022. "Percolation transition prescribes protein size-specific barrier to passive transport through the nuclear pore complex," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-023-40227-8. 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.