title: Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation.
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.
authors.affiliation: Institutes of Evolution, Immunology, and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Lythgoe
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Morrison
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Read
authors.forename: J David
authors.initials: JD
authors.lastname: Barry
mesh_terms: D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000032:analysis*; D008962:Models, Theoretical; D014345:Trypanosoma / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics
chemical_list: D000953:Antigens, Protozoan; D014643:Variant Surface Glycoproteins, Trypanosoma