Author:
GALINSKI M. R.,LAPP S. A.,PETERSON M. S.,AY F.,JOYNER C. J.,LE ROCH K. G.,FONSECA L. L.,VOIT E. O.,
Abstract
SUMMARYAntigenic variation in malaria was discovered inPlasmodium knowlesistudies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as theP. knowlesiSchizont Infected Cell Agglutination (SICA) antigens and theP. falciparumErythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by theSICAvarandvarmultigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens inP. knowlesirequires a splenic component, and specific antibodies are necessary for variant antigen switch eventsin 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 withP. knowlesiinfection 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 ofP. knowlesi– macaque model systems and summarizing exciting new progress in this area of research.
Publisher
Cambridge University Press (CUP)
Subject
Infectious Diseases,Animal Science and Zoology,Parasitology
Cited by
29 articles.
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