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

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, Timothy G. Myers, Shengfa Liu, Carole A. Long, Jian Li () and Xin-zhuan Su ()
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Sethu C. Nair: National Institutes of Health
Ruixue Xu: Xiamen University
Sittiporn Pattaradilokrat: National Institutes of Health
Jian Wu: National Institutes of Health
Yanwei Qi: National Institutes of Health
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

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00267-3

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