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Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections

Author

Listed:
  • Angela M. Early

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health)

  • Marc Lievens

    (GSK Vaccines)

  • Bronwyn L. MacInnis

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health)

  • Christian F. Ockenhouse

    (PATH Malaria Vaccine Initiative)

  • Sarah K. Volkman

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health
    School of Nursing and Health Sciences)

  • Samuel Adjei

    (Kwame Nkrumah University of Science and Technology)

  • Tsiri Agbenyega

    (Kwame Nkrumah University of Science and Technology)

  • Daniel Ansong

    (Kwame Nkrumah University of Science and Technology)

  • Stacey Gondi

    (KEMRI–Walter Reed Project)

  • Brian Greenwood

    (London School of Hygiene and Tropical Medicine)

  • Mary Hamel

    (KEMRI/CDC Research and Public Health Collaboration)

  • Chris Odero

    (KEMRI/CDC Research and Public Health Collaboration)

  • Kephas Otieno

    (KEMRI/CDC Research and Public Health Collaboration)

  • Walter Otieno

    (KEMRI–Walter Reed Project)

  • Seth Owusu-Agyei

    (London School of Hygiene and Tropical Medicine
    Kintampo Health Research Centre
    University of Health and Allied Science)

  • Kwaku Poku Asante

    (Kintampo Health Research Centre)

  • Hermann Sorgho

    (Nanoro, Burkina Faso/Institute of Tropical Medicine)

  • Lucas Tina

    (KEMRI–Walter Reed Project)

  • Halidou Tinto

    (Nanoro, Burkina Faso/Institute of Tropical Medicine)

  • Innocent Valea

    (Nanoro, Burkina Faso/Institute of Tropical Medicine)

  • Dyann F. Wirth

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health)

  • Daniel E. Neafsey

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health)

Abstract

Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasite Plasmodium falciparum using haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses to P. falciparum act in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.

Suggested Citation

  • Angela M. Early & Marc Lievens & Bronwyn L. MacInnis & Christian F. Ockenhouse & Sarah K. Volkman & Samuel Adjei & Tsiri Agbenyega & Daniel Ansong & Stacey Gondi & Brian Greenwood & Mary Hamel & Chris, 2018. "Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03807-7
    DOI: 10.1038/s41467-018-03807-7
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    Cited by:

    1. Selina Bopp & Charisse Flerida A. Pasaje & Robert L. Summers & Pamela Magistrado-Coxen & Kyra A. Schindler & Victoriano Corpas-Lopez & Tomas Yeo & Sachel Mok & Sumanta Dey & Sebastian Smick & Armiyaw , 2023. "Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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