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

Katrina A. Lythgoe, Liam J. Morrison, Andrew F. Read, J. David Barry

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8095-8100
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number19
DOIs
StatePublished - May 8 2007

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Antigenic Variation
Intrinsic Factor
Trypanosomiasis
Membrane Glycoproteins
Parasites
Infection
Parasitemia
Surface Antigens
Genes
Immunity
Theoretical Models
Growth

All Science Journal Classification (ASJC) codes

  • General

Cite this

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Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation. / Lythgoe, Katrina A.; Morrison, Liam J.; Read, Andrew F.; Barry, J. David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 19, 08.05.2007, p. 8095-8100.

Research output: Contribution to journalArticle

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