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Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles

Author

Listed:
  • Hannah O. Ajoge

    (Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology)

  • Tyler M. Renner

    (University of Ottawa)

  • Kasandra Bélanger

    (University of Ottawa)

  • Matthew Greig

    (University of Ottawa)

  • Samar Dankar

    (University of Ottawa)

  • Hinissan P. Kohio

    (Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology)

  • Macon D. Coleman

    (Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology)

  • Emmanuel Ndashimye

    (Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology)

  • Eric J. Arts

    (Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology)

  • Marc-André Langlois

    (University of Ottawa
    Ottawa Center for Infection, Immunity and Inflammation (CI3))

  • Stephen D. Barr

    (Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology)

Abstract

APOBEC3 (A3) proteins are host-encoded deoxycytidine deaminases that provide an innate immune barrier to retroviral infection, notably against HIV-1. Low levels of deamination are believed to contribute to the genetic evolution of HIV-1, while intense catalytic activity of these proteins can induce catastrophic hypermutation in proviral DNA leading to near-total HIV-1 restriction. So far, little is known about how A3 cytosine deaminases might impact HIV-1 proviral DNA integration sites in human chromosomal DNA. Using a deep sequencing approach, we analyze the influence of catalytic active and inactive APOBEC3F and APOBEC3G on HIV-1 integration site selections. Here we show that DNA editing is detected at the extremities of the long terminal repeat regions of the virus. Both catalytic active and non-catalytic A3 mutants decrease insertions into gene coding sequences and increase integration sites into SINE elements, oncogenes and transcription-silencing non-B DNA features. Our data implicates A3 as a host factor influencing HIV-1 integration site selection and also promotes what appears to be a more latent expression profile.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35379-y
    DOI: 10.1038/s41467-022-35379-y
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    References listed on IDEAS

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