IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v424y2003i6944d10.1038_nature01707.html
   My bibliography  Save this article

The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA

Author

Listed:
  • Hui Zhang

    (Thomas Jefferson University)

  • Bin Yang

    (Thomas Jefferson University)

  • Roger J. Pomerantz

    (Thomas Jefferson University)

  • Chune Zhang

    (Thomas Jefferson University)

  • Shyamala C. Arunachalam

    (Thomas Jefferson University)

  • Ling Gao

    (Thomas Jefferson University)

Abstract

High mutation frequency during reverse transcription has a principal role in the genetic variation of primate lentiviral populations. It is the main driving force for the generation of drug resistance and the escape from immune surveillance. G to A hypermutation is one of the characteristics of primate lentiviruses, as well as other retroviruses, during replication in vivo and in cell culture1,2,3,4,5,6. The molecular mechanisms of this process, however, remain to be clarified. Here, we demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G; APOBEC3G)7,8, an endogenous inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is able to induce G to A hypermutation in newly synthesized viral DNA. This effect can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that this viral DNA mutator is a viral defence mechanism in host cells that may induce either lethal hypermutation or instability of the incoming nascent viral reverse transcripts, which could account for the Vif-defective phenotype. Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations.

Suggested Citation

  • Hui Zhang & Bin Yang & Roger J. Pomerantz & Chune Zhang & Shyamala C. Arunachalam & Ling Gao, 2003. "The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA," Nature, Nature, vol. 424(6944), pages 94-98, July.
    • Handle: RePEc:nat:nature:v:424:y:2003:i:6944:d:10.1038_nature01707
    DOI: 10.1038/nature01707
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature01707
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature01707?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Beth K Thielen & Kevin C Klein & Lorne W Walker & Mary Rieck & Jane H Buckner & Garrett W Tomblingson & Jaisri R Lingappa, 2007. "T Cells Contain an RNase-Insensitive Inhibitor of APOBEC3G Deaminase Activity," PLOS Pathogens, Public Library of Science, vol. 3(9), pages 1-15, September.
    2. Hanjing Yang & Kyumin Kim & Shuxing Li & Josue Pacheco & Xiaojiang S. Chen, 2022. "Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Vanessa B Soros & Wes Yonemoto & Warner C Greene, 2007. "Newly Synthesized APOBEC3G Is Incorporated into HIV Virions, Inhibited by HIV RNA, and Subsequently Activated by RNase H," PLOS Pathogens, Public Library of Science, vol. 3(2), pages 1-16, February.
    4. Iraj Hosseini & Feilim Mac Gabhann, 2012. "Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy," PLOS Computational Biology, Public Library of Science, vol. 8(2), pages 1-17, February.
    5. Patric Jern & Rebecca A Russell & Vinay K Pathak & John M Coffin, 2009. "Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance," PLOS Pathogens, Public Library of Science, vol. 5(4), pages 1-9, April.

    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:nature:v:424:y:2003:i:6944:d:10.1038_nature01707. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.