Trends in Parasitology
Volume 31, Issue 8, August 2015, Pages 346-349
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Quantitative sequencing confirms VSG diversity as central to immune evasion by Trypanosoma brucei

https://doi.org/10.1016/j.pt.2015.05.001Get rights and content

Antigenic variation is central to the virulence of African trypanosomes, where the VSG coat is used to evade the host immune system. Recent advances in technology have now allowed more secrets of this system to emerge, with the surprising insight that a broad repertoire of VSGs is rapidly expressed. This has major implications for how the parasite must evade the host immune response.

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Acknowledgements

We thank J. David Barry for several discussions on this topic.

References (10)

  • L.J. Morrison

    Probabilistic order in antigenic variation of Trypanosoma brucei

    Int. J. Parasitol.

    (2005)
  • K.W. Deitsch

    Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens

    Nat. Rev. Microbiol.

    (2009)
  • L. Marcello et al.

    Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure

    Genome Res.

    (2007)
  • L. Glover

    Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control

    Cell. Microbiol.

    (2013)
  • L. Glover

    DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in African trypanosomes

    PLoS Pathog.

    (2013)
There are more references available in the full text version of this article.

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