IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40000-x.html
   My bibliography  Save this article

HIV-1 promotes ubiquitination of the amyloidogenic C-terminal fragment of APP to support viral replication

Author

Listed:
  • Feng Gu

    (Northwestern University Feinberg School of Medicine)

  • Marie Boisjoli

    (Northwestern University Feinberg School of Medicine)

  • Mojgan H. Naghavi

    (Northwestern University Feinberg School of Medicine)

Abstract

HIV-1 replication in macrophages and microglia involves intracellular assembly and budding into modified subsets of multivesicular bodies (MVBs), which support both viral persistence and spread. However, the cellular factors that regulate HIV-1’s vesicular replication remain poorly understood. Recently, amyloid precursor protein (APP) was identified as an inhibitor of HIV-1 replication in macrophages and microglia via an unknown mechanism. Here, we show that entry of HIV-1 Gag into MVBs is blocked by the amyloidogenic C-terminal fragment of APP, “C99”, but not by the non-amyloidogenic product, “C83”. To counter this, Gag promotes multi-site ubiquitination of C99 which controls both exocytic sorting of MVBs and further processing of C99 into toxic amyloids. Processing of C99, entry of Gag into MVBs and release of infectious virus could be suppressed by expressing ubiquitination-defective C99 or by γ-secretase inhibitor treatment, suggesting that APP’s amyloidogenic pathway functions to sense and suppress HIV-1 replication in macrophages and microglia.

Suggested Citation

  • Feng Gu & Marie Boisjoli & Mojgan H. Naghavi, 2023. "HIV-1 promotes ubiquitination of the amyloidogenic C-terminal fragment of APP to support viral replication," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40000-x
    DOI: 10.1038/s41467-023-40000-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40000-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40000-x?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. Etienne Morel & Zeina Chamoun & Zofia M. Lasiecka & Robin B. Chan & Rebecca L. Williamson & Christopher Vetanovetz & Claudia Dall’Armi & Sabrina Simoes & Kimberly S. Point Du Jour & Brian D. McCabe & , 2013. "Phosphatidylinositol-3-phosphate regulates sorting and processing of amyloid precursor protein through the endosomal system," Nature Communications, Nature, vol. 4(1), pages 1-13, October.
    2. Alison Abbott, 2020. "Are infections seeding some cases of Alzheimer’s disease?," Nature, Nature, vol. 587(7832), pages 22-25, November.
    3. Qingqing Chai & Vladimir Jovasevic & Viacheslav Malikov & Yosef Sabo & Scott Morham & Derek Walsh & Mojgan H. Naghavi, 2017. "HIV-1 counteracts an innate restriction by amyloid precursor protein resulting in neurodegeneration," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    4. Viacheslav Malikov & Eveline Santos da Silva & Vladimir Jovasevic & Geoffrey Bennett & Daniel A. de Souza Aranha Vieira & Bianca Schulte & Felipe Diaz-Griffero & Derek Walsh & Mojgan H. Naghavi, 2015. "HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    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. Satra Nim & Darren M. O’Hara & Carles Corbi-Verge & Albert Perez-Riba & Kazuko Fujisawa & Minesh Kapadia & Hien Chau & Federica Albanese & Grishma Pawar & Mitchell L. Snoo & Sophie G. Ngana & Jisun Ki, 2023. "Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Hernán Ramos & Lucrecia Moreno & María Gil & Gemma García-Lluch & José Sendra-Lillo & Mónica Alacreu, 2021. "Pharmacists’ Knowledge of Factors Associated with Dementia: The A-to-Z Dementia Knowledge List," IJERPH, MDPI, vol. 18(19), pages 1-18, September.
    3. Taniya Bhardwaj & Kundlik Gadhave & Shivani K. Kapuganti & Prateek Kumar & Zacharias Faidon Brotzakis & Kumar Udit Saumya & Namyashree Nayak & Ankur Kumar & Richa Joshi & Bodhidipra Mukherjee & Aparna, 2023. "Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Annie Lee & Chandana Kondapalli & Daniel M. Virga & Tommy L. Lewis & So Yeon Koo & Archana Ashok & Georges Mairet-Coello & Sebastien Herzig & Marc Foretz & Benoit Viollet & Reuben Shaw & Andrew Sproul, 2022. "Aβ42 oligomers trigger synaptic loss through CAMKK2-AMPK-dependent effectors coordinating mitochondrial fission and mitophagy," Nature Communications, Nature, vol. 13(1), pages 1-20, 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_s41467-023-40000-x. 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.