Research area: synthetic_biology

Faster Growth With Shorter Antigens Explains A VSG Hierarchy During African Trypanosome Infections: A Feint Attack By Parasites

Created on 26th April 2017

Dianbo Liu; Luca Albergante; David Horn; Timothy Newman;

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.

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