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Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts

Author

Listed:
  • Bastien Mangeat

    (Department of Genetics and Microbiology)

  • Priscilla Turelli

    (Department of Genetics and Microbiology)

  • Gersende Caron

    (Department of Medicine)

  • Marc Friedli

    (Department of Genetics and Microbiology
    University of Geneva)

  • Luc Perrin

    (Department of Medicine)

  • Didier Trono

    (Department of Genetics and Microbiology
    University of Geneva)

Abstract

Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes1,2,3,4. When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA5,6,7. APOBEC family members also have potent DNA mutator activity through dC deamination8; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.

Suggested Citation

  • Bastien Mangeat & Priscilla Turelli & Gersende Caron & Marc Friedli & Luc Perrin & Didier Trono, 2003. "Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts," Nature, Nature, vol. 424(6944), pages 99-103, July.
    • Handle: RePEc:nat:nature:v:424:y:2003:i:6944:d:10.1038_nature01709
    DOI: 10.1038/nature01709
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    Cited by:

    1. Hannah O. Ajoge & Tyler M. Renner & Kasandra Bélanger & Matthew Greig & Samar Dankar & Hinissan P. Kohio & Macon D. Coleman & Emmanuel Ndashimye & Eric J. Arts & Marc-André Langlois & Stephen D. Barr, 2023. "Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Fumiaki Ito & Ana L. Alvarez-Cabrera & Kyumin Kim & Z. Hong Zhou & Xiaojiang S. Chen, 2023. "Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Hanjing Yang & Josue Pacheco & Kyumin Kim & Ayub Bokani & Fumiaki Ito & Diako Ebrahimi & Xiaojiang S. Chen, 2024. "Molecular mechanism for regulating APOBEC3G DNA editing function by the non-catalytic domain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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