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Faster growth with shorter antigens explains a VSG hierarchy during African trypanosome infections: a feint attack by parasites

Dianbo Liu, Luca Albergante, David Horn, Timothy Newman
doi: https://doi.org/10.1101/131029
Dianbo Liu
1School of Life Sciences, University of Dundee, Dundee, UK
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Luca Albergante
1School of Life Sciences, University of Dundee, Dundee, UK
2U900, Institut Curie, 75005, France
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David Horn
1School of Life Sciences, University of Dundee, Dundee, UK
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Timothy Newman
1School of Life Sciences, University of Dundee, Dundee, UK
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Abstract

The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that periodically come to dominate in vivo display a hierarchy, but how this hierarchy arises is not well-understood. Combining publicly available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, revealing an inverse correlation between VSG length and trypanosome growth-rate. Our analysis indicates that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger an effective immune response. Subsequent elimination of faster-growing parasites then allows slower parasites with longer VSGs to accumulate. This interaction between the host and parasite is able by itself to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection, representing a ‘feint attack’ diversion tactic utilised during infection by these persistent parasites to out-maneuver the host immune system.

Significance Statement The protozoan parasite Trypanosoma brucei causes devastating and lethal diseases in humans and livestock. This parasite continuously evades the host adaptive immune response by drawing on a library of variant surface proteins but the mechanisms determining the timing of surface protein – host interactions are not understood. We report a simple mechanism, based on differential growth of parasites with surface proteins of different lengths, which can explain the hierarchy of variants over time. This allows parasites to evade host immune responses for extended timeframes using limited cohorts of surface proteins. We liken this strategy to a military ‘feint attack’, that enhances the parasites ability to evade the host immune response. A similar mechanism may also operate in other important pathogens.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 26, 2017.
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Faster growth with shorter antigens explains a VSG hierarchy during African trypanosome infections: a feint attack by parasites
Dianbo Liu, Luca Albergante, David Horn, Timothy Newman
bioRxiv 131029; doi: https://doi.org/10.1101/131029
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Faster growth with shorter antigens explains a VSG hierarchy during African trypanosome infections: a feint attack by parasites
Dianbo Liu, Luca Albergante, David Horn, Timothy Newman
bioRxiv 131029; doi: https://doi.org/10.1101/131029

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