Host-mediated Selection Impacts the Diversity of Plasmodium Falciparum Antigens Within Infections

Nat Commun. 2018 Apr 11;9(1):1381. doi: 10.1038/s41467-018-03807-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa South of the Sahara / epidemiology
  • Alleles
  • Antigens, Protozoan / genetics*
  • Antigens, Protozoan / immunology
  • Child, Preschool
  • Female
  • Gene Expression Regulation
  • Gene Frequency
  • Genetic Variation
  • Haplotypes*
  • Host-Parasite Interactions*
  • Humans
  • Infant
  • Linkage Disequilibrium
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / genetics*
  • Malaria, Falciparum / immunology
  • Male
  • Multigene Family
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / immunology
  • Plasmodium falciparum / pathogenicity
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology

Substances

  • Antigens, Protozoan
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan
  • serine repeat antigen, Plasmodium
  • thrombospondin-related adhesive protein, protozoan