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Author Notes:

Corresponding author: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta GA, USA. E-mail: mary.galinski@emory.edu

The authors would like to thank Jeremy D. DeBarry and Jessica C. Kissinger for review of the P. knowlesi nuclear genome information provided in Table 2, the Wellcome Trust Sanger Institute and GeneDB for making their P. knowlesi genome sequence (version 2) and annotation available to the community, PlasmoDB for analysis tools, and John W. Barnwell for his enthusiastic review of the manuscript.

Subjects:

Research Funding:

This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases; National Institutes of Health, Department of Health and Human Services (M.R.G., contract number HHSN272201200031C), (M.R.G., grant number R01AI065961), (K.G.L.R., grant number R01AI06775); The National Center for Research Resources (Y.N.P.R.C., grant number ORIP/OD P51OD011132); The University of California, Riverside (K.G.L.R., NIFA-Hatch-225935); and Institute Leadership Funds from La Jolla Institute for Allergy and Immunology (F.A.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Parasitology
  • SIC Avar genes
  • var genes
  • Plasmodium falciparum
  • epigenetics
  • mathematical models
  • systems biology
  • multiomics
  • host-pathogen interactions
  • longitudinal infections
  • macaques
  • FALCIPARUM-INFECTED ERYTHROCYTES
  • MUTUALLY EXCLUSIVE EXPRESSION
  • LONG NONCODING RNAS
  • VAR GENE-EXPRESSION
  • RED-BLOOD-CELLS
  • VARIANT ANTIGEN
  • VIRULENCE GENES
  • SURFACE-ANTIGENS
  • MEMBRANE PROTEIN-1
  • EPIGENETIC MEMORY

Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria

Tools:

Journal Title:

Parasitology

Volume:

Volume 145, Number 1

Publisher:

, Pages 85-100

Type of Work:

Article | Final Publisher PDF

Abstract:

Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi – macaque model systems and summarizing exciting new progress in this area of research.

Copyright information:

© Cambridge University Press 2017

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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