IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51971-w.html
   My bibliography  Save this article

HIV-1 adapts to lost IP6 coordination through second-site mutations that restore conical capsid assembly

Author

Listed:
  • Alex Kleinpeter

    (National Cancer Institute)

  • Donna L. Mallery

    (Francis Crick Avenue)

  • Nadine Renner

    (Francis Crick Avenue)

  • Anna Albecka

    (Francis Crick Avenue)

  • J. Ole Klarhof

    (Francis Crick Avenue)

  • Eric O. Freed

    (National Cancer Institute)

  • Leo C. James

    (Francis Crick Avenue)

Abstract

The HIV-1 capsid is composed of capsid (CA) protein hexamers and pentamers (capsomers) that contain a central pore hypothesised to regulate capsid assembly and facilitate nucleotide import early during post-infection. These pore functions are mediated by two positively charged rings created by CA Arg-18 (R18) and Lys-25 (K25). Here we describe the forced evolution of viruses containing mutations in R18 and K25. Whilst R18 mutants fail to replicate, K25A viruses acquire compensating mutations that restore nearly wild-type replication fitness. These compensating mutations, which rescue reverse transcription and infection without reintroducing lost pore charges, map to three adaptation hot-spots located within and between capsomers. The second-site suppressor mutations act by restoring the formation of pentamers lost upon K25 mutation, enabling closed conical capsid assembly both in vitro and inside virions. These results indicate that there is no intrinsic requirement for K25 in either nucleotide import or capsid assembly. We propose that whilst HIV-1 must maintain a precise hexamer:pentamer equilibrium for proper capsid assembly, compensatory mutations can tune this equilibrium to restore fitness lost by mutation of the central pore.

Suggested Citation

  • Alex Kleinpeter & Donna L. Mallery & Nadine Renner & Anna Albecka & J. Ole Klarhof & Eric O. Freed & Leo C. James, 2024. "HIV-1 adapts to lost IP6 coordination through second-site mutations that restore conical capsid assembly," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51971-w
    DOI: 10.1038/s41467-024-51971-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51971-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51971-w?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. Robert A. Dick & Kaneil K. Zadrozny & Chaoyi Xu & Florian K. M. Schur & Terri D. Lyddon & Clifton L. Ricana & Jonathan M. Wagner & Juan R. Perilla & Barbie K. Ganser-Pornillos & Marc C. Johnson & Owen, 2018. "Inositol phosphates are assembly co-factors for HIV-1," Nature, Nature, vol. 560(7719), pages 509-512, August.
    2. 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.
    3. David A. Jacques & William A. McEwan & Laura Hilditch & Amanda J. Price & Greg J. Towers & Leo C. James, 2016. "HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis," Nature, Nature, vol. 536(7616), pages 349-353, August.
    4. Robert A. Dick & Kaneil K. Zadrozny & Chaoyi Xu & Florian K. M. Schur & Terri D. Lyddon & Clifton L. Ricana & Jonathan M. Wagner & Juan R. Perilla & Barbie K. Ganser-Pornillos & Marc C. Johnson & Owen, 2018. "Author Correction: Inositol phosphates are assembly co-factors for HIV-1," Nature, Nature, vol. 563(7731), pages 22-22, November.
    5. 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. 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.
    2. Anna-Sophia Krebs & Hsuan-Fu Liu & Ye Zhou & Juan S. Rey & Lev Levintov & Juan Shen & Andrew Howe & Juan R. Perilla & Alberto Bartesaghi & Peijun Zhang, 2023. "Molecular architecture and conservation of an immature human endogenous retrovirus," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Sucharita Sarkar & Kaneil K. Zadrozny & Roman Zadorozhnyi & Ryan W. Russell & Caitlin M. Quinn & Alex Kleinpeter & Sherimay Ablan & Hamed Meshkin & Juan R. Perilla & Eric O. Freed & Barbie K. Ganser-P, 2023. "Structural basis of HIV-1 maturation inhibitor binding and activity," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Ruochen Ouyang & Ana Rita Costa & C. Keith Cassidy & Aleksandra Otwinowska & Vera C. J. Williams & Agnieszka Latka & Phill J. Stansfeld & Zuzanna Drulis-Kawa & Yves Briers & Daniël M. Pelt & Stan J. J, 2022. "High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. 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.

    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:15:y:2024:i:1:d:10.1038_s41467-024-51971-w. 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.