IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-022-35379-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35379-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35379-y?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. Ann M. Sheehy & Nathan C. Gaddis & Jonathan D. Choi & Michael H. Malim, 2002. "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein," Nature, Nature, vol. 418(6898), pages 646-650, August.
    2. Daniel P. Maskell & Ludovic Renault & Erik Serrao & Paul Lesbats & Rishi Matadeen & Stephen Hare & Dirk Lindemann & Alan N. Engelman & Alessandro Costa & Peter Cherepanov, 2015. "Structural basis for retroviral integration into nucleosomes," Nature, Nature, vol. 523(7560), pages 366-369, July.
    3. 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.
    4. Bruna Marini & Attila Kertesz-Farkas & Hashim Ali & Bojana Lucic & Kamil Lisek & Lara Manganaro & Sandor Pongor & Roberto Luzzati & Alessandra Recchia & Fulvio Mavilio & Mauro Giacca & Marina Lusic, 2015. "Nuclear architecture dictates HIV-1 integration site selection," Nature, Nature, vol. 521(7551), pages 227-231, 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. 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.
    2. 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.
    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. 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.
    5. 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.
    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. Gayan Senavirathne & James London & Anne Gardner & Richard Fishel & Kristine E. Yoder, 2023. "DNA strand breaks and gaps target retroviral intasome binding and integration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Weijing Yang & Hong Wang & Zhaolong Li & Lihua Zhang & Jianhui Liu & Frank Kirchhoff & Chen Huan & Wenyan Zhang, 2024. "RPLP1 restricts HIV-1 transcription by disrupting C/EBPβ binding to the LTR," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Diako Ebrahimi & Hamid Alinejad-Rokny & Miles P Davenport, 2014. "Insights into the Motif Preference of APOBEC3 Enzymes," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-9, January.
    10. Monica Naughtin & Zofia Haftek-Terreau & Johan Xavier & Sam Meyer & Maud Silvain & Yan Jaszczyszyn & Nicolas Levy & Vincent Miele & Mohamed Salah Benleulmi & Marc Ruff & Vincent Parissi & Cédric Vaill, 2015. "DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-28, June.
    11. Li Wang & Jiali Yu & Zishuo Yu & Qianmin Wang & Wanjun Li & Yulei Ren & Zhenguo Chen & Shuang He & Yanhui Xu, 2022. "Structure of nucleosome-bound human PBAF complex," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    12. Takahide Kouno & Satoshi Shibata & Megumi Shigematsu & Jaekyung Hyun & Tae Gyun Kim & Hiroshi Matsuo & Matthias Wolf, 2023. "Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Jing Ma & Xiaoyu Li & Jian Xu & Quan Zhang & Zhenlong Liu & Pingping Jia & Jinming Zhou & Fei Guo & Xuefu You & Liyan Yu & Lixun Zhao & Jiandong Jiang & Shan Cen, 2013. "The Roles of APOBEC3G Complexes in the Incorporation of APOBEC3G into HIV-1," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-9, October.
    14. Atanu Maiti & Adam K. Hedger & Wazo Myint & Vanivilasini Balachandran & Jonathan K. Watts & Celia A. Schiffer & Hiroshi Matsuo, 2022. "Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    15. Guillermo Abascal-Palacios & Laura Jochem & Carlos Pla-Prats & Fabienne Beuron & Alessandro Vannini, 2021. "Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    16. Joseph Hiatt & Judd F. Hultquist & Michael J. McGregor & Mehdi Bouhaddou & Ryan T. Leenay & Lacy M. Simons & Janet M. Young & Paige Haas & Theodore L. Roth & Victoria Tobin & Jason A. Wojcechowskyj & , 2022. "A functional map of HIV-host interactions in primary human T cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Allison Ballandras-Colas & Vidya Chivukula & Dominika T. Gruszka & Zelin Shan & Parmit K. Singh & Valerie E. Pye & Rebecca K. McLean & Gregory J. Bedwell & Wen Li & Andrea Nans & Nicola J. Cook & Hind, 2022. "Multivalent interactions essential for lentiviral integrase function," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-022-35379-y. 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.