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A Plasmodium yoelii HECT-like E3 ubiquitin ligase regulates parasite growth and virulence

Author

Listed:
  • Sethu C. Nair

    (National Institutes of Health)

  • Ruixue Xu

    (Xiamen University)

  • Sittiporn Pattaradilokrat

    (National Institutes of Health
    Chulalongkorn University)

  • Jian Wu

    (National Institutes of Health)

  • Yanwei Qi

    (National Institutes of Health
    Xiamen University)

  • Martine Zilversmit

    (National Institutes of Health)

  • Sundar Ganesan

    (National Institutes of Health)

  • Vijayaraj Nagarajan

    (National Institutes of Health)

  • Richard T. Eastman

    (National Institutes of Health)

  • Marlene S. Orandle

    (National Institutes of Health)

  • John C. Tan

    (University of Notre Dame)

  • Timothy G. Myers

    (National Institutes of Health)

  • Shengfa Liu

    (Xiamen University)

  • Carole A. Long

    (National Institutes of Health)

  • Jian Li

    (Xiamen University)

  • Xin-zhuan Su

    (National Institutes of Health
    Xiamen University)

Abstract

Infection of mice with strains of Plasmodium yoelii parasites can result in different pathology, but molecular mechanisms to explain this variation are unclear. Here we show that a P. yoelii gene encoding a HECT-like E3 ubiquitin ligase (Pyheul) influences parasitemia and host mortality. We genetically cross two lethal parasites with distinct disease phenotypes, and identify 43 genetically diverse progeny by typing with microsatellites and 9230 single-nucleotide polymorphisms. A genome-wide quantitative trait loci scan links parasite growth and host mortality to two major loci on chromosomes 1 and 7 with LOD (logarithm of the odds) scores = 6.1 and 8.1, respectively. Allelic exchange of partial sequences of Pyheul in the chromosome 7 locus and modification of the gene expression alter parasite growth and host mortality. This study identifies a gene that may have a function in parasite growth, virulence, and host–parasite interaction, and therefore could be a target for drug or vaccine development.

Suggested Citation

  • Sethu C. Nair & Ruixue Xu & Sittiporn Pattaradilokrat & Jian Wu & Yanwei Qi & Martine Zilversmit & Sundar Ganesan & Vijayaraj Nagarajan & Richard T. Eastman & Marlene S. Orandle & John C. Tan & Timoth, 2017. "A Plasmodium yoelii HECT-like E3 ubiquitin ligase regulates parasite growth and virulence," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00267-3
    DOI: 10.1038/s41467-017-00267-3
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