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

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 Odero, Kephas Otieno, Walter Otieno, Seth Owusu-Agyei, Kwaku Poku Asante, Hermann Sorgho, Lucas Tina, Halidou Tinto, Innocent ValeaDyann F. Wirth, Daniel E. Neafsey

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
Article number1381
JournalNature Communications
Volume9
Number of pages10
ISSN2041-1723
DOIs
Publication statusPublished - 2018

Keywords

  • VACCINE-CANDIDATE ANTIGENS
  • ALTERED PEPTIDE LIGANDS
  • T-CELL RECOGNITION
  • CIRCUMSPOROZOITE PROTEIN
  • MALARIA PARASITE
  • POPULATION STRUCTURES
  • ACQUIRED-IMMUNITY
  • GENETIC DIVERSITY
  • EPITOPES
  • ENDEMICITY

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