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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
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    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.

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