Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Lythgoe, K., Morrison, L., Read, A. and Barry, J. (2007) Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation. Proceedings of the National Academy of Sciences of the United States of America, 104(19), pp. 8095-8100. (doi: 10.1073/pnas.0606206104)

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Abstract

Pathogens often persist during infection because of antigenic variation in which they evade immunity by switching between distinct surface antigen variants. A central question is how ordered appearance of variants, an important determinant of chronicity, is achieved. Theories suggest that it results directly from a complex pattern of transition connectivity between variants or indirectly from effects such as immune cross-reactivity or differential variant growth rates. Using a mathematical model based only on known infection variables, we show that order in trypanosome infections can be explained more parsimoniously by a simpler combination of two key parasite-intrinsic factors: differential activation rates of parasite variant surface glycoprotein (VSG) genes and density-dependent parasite differentiation. The model outcomes concur with empirical evidence that several variants are expressed simultaneously and that parasitaemia peaks correlate with VSG genes within distinct activation probability groups. Our findings provide a possible explanation for the enormity of the recently sequenced VSG silent archive and have important implications for field transmission.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barry, Professor J
Authors: Lythgoe, K., Morrison, L., Read, A., and Barry, J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490

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