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Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity

Author

Listed:
  • Jean Popovici

    (Institut Pasteur du Cambodge, Institut Pasteur)

  • Camille Roesch

    (Institut Pasteur du Cambodge, Institut Pasteur)

  • Lenore L. Carias

    (Case Western Reserve University, School of Medicine)

  • Nimol Khim

    (Institut Pasteur du Cambodge, Institut Pasteur)

  • Saorin Kim

    (Institut Pasteur du Cambodge, Institut Pasteur)

  • Amelie Vantaux

    (Institut Pasteur du Cambodge, Institut Pasteur)

  • Ivo Mueller

    (Institut Pasteur
    The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne, Parkville)

  • Chetan E. Chitnis

    (Institut Pasteur)

  • Christopher L. King

    (Case Western Reserve University, School of Medicine
    Cleveland VA Medical Center)

  • Benoit Witkowski

    (Institut Pasteur du Cambodge, Institut Pasteur)

Abstract

Antigenic variation, the capacity to produce a range of variable antigens, is a well-described strategy of Plasmodium and other parasites to evade host immunity. Here, we show that gene amplification is an additional evasion mechanism used by Plasmodium vivax to escape humoral immunity targeting PvDBP, the key ligand involved in reticulocyte invasion. PvDBP gene amplification leads to increased mRNA levels and protects P. vivax in vitro against invasion inhibitory human monoclonal antibodies targeting a conserved binding domain of DBP. Patient samples suggest that parasites with increased pvdbp copy number are able to infect individuals with naturally acquired antibodies highly blocking the binding of PvDBP to the Duffy receptor. These results show that gene copy number variation affect the parasite’s ability to evade anti-PvDBP humoral immunity.

Suggested Citation

  • Jean Popovici & Camille Roesch & Lenore L. Carias & Nimol Khim & Saorin Kim & Amelie Vantaux & Ivo Mueller & Chetan E. Chitnis & Christopher L. King & Benoit Witkowski, 2020. "Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14574-9
    DOI: 10.1038/s41467-020-14574-9
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