Emerging challenges in understanding trypanosome antigenic variation

McCulloch, R. , Cobbold, C. A. , Figueiredo, L., Jackson, A., Morrison, L. J., Mugnier, M. R., Papavasiliou, N., Schnaufer, A. and Matthews, K. (2017) Emerging challenges in understanding trypanosome antigenic variation. Emerging Topics in Life Sciences, 1(6), pp. 585-592. (doi:10.1042/ETLS20170104)

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Abstract

Many pathogens evade host immunity by periodically changing the proteins they express on their surface — a phenomenon termed antigenic variation. An extreme form of antigenic variation, based around switching the composition of a variant surface glycoprotein (VSG) coat, is exhibited by the African trypanosome Trypanosoma brucei, which causes human disease. The molecular details of VSG switching in T. brucei have been extensively studied over the last three decades, revealing in increasing detail the machinery and mechanisms by which VSG expression is controlled and altered. However, several key components of the models of T. brucei antigenic variation that have emerged have been challenged through recent discoveries. These discoveries include new appreciation of the importance of gene mosaics in generating huge levels of new VSG variants, the contributions of parasite development and body compartmentation in the host to the infection dynamics and, finally, potential differences in the strategies of antigenic variation and host infection used by the crucial livestock trypanosomes T. congolense and T. vivax. This review will discuss all these observations, which raise questions regarding how secure the existing models of trypanosome antigenic variation are. In addition, we will discuss the importance of continued mathematical modelling to understand the purpose of this widespread immune survival process.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cobbold, Dr Christina and McCulloch, Professor Richard
Authors: McCulloch, R., Cobbold, C. A., Figueiredo, L., Jackson, A., Morrison, L. J., Mugnier, M. R., Papavasiliou, N., Schnaufer, A., and Matthews, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Science and Engineering > School of Mathematics and Statistics > Mathematics
Journal Name:Emerging Topics in Life Sciences
Publisher:Portland Press
ISSN:2397-8554
ISSN (Online):2397-8562
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Emerging Topics in Life Sciences 1(6):585-592
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
515891Chromosomal recombination and repair in African trypanosomesRichard McCullochWellcome Trust (WELLCOTR)089172/Z/09/ZIII - PARASITOLOGY
606431Kinase dependent control of DNA replication and repair as a drug target in Trypanosoma brucei.Richard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/K006495/1III - PARASITOLOGY
68706114CONFAP Understanding diverged genome repair and replication functions in trypanosomatid parasitesRichard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/M028909/1III - PARASITOLOGY
716221How do common and diverged features of the replicative stress response shape the biology of TriTrypRichard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/N016165/1III - PARASITOLOGY
730011Mathematical Theory and Biological Applications of DiversityRichard ReeveBiotechnology and Biological Sciences Research Council (BBSRC)BB/P004202/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED

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