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Tracking the in vivo dynamics of antigenic variation In Trypanosoma brucei
Author(s) -
Mugnier Monica,
Cross George A.M.,
Papavasiliou F. Nina
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.238.2
Subject(s) - trypanosoma brucei , biology , antigenic variation , genetics , gene , genome , population , computational biology , demography , sociology
Trypanosoma brucei changes its dense variant surface glycoprotein (VSG) surface coat to avoid detection by the immune system of its mammalian host. The dynamics of antigenic variation during T. brucei infection, a process that takes advantage of a genomic repertoire of over 2000 different VSG‐encoding genes, are poorly understood. How many variants appear over the course of an infection? Is there a pattern to VSG expression over time? Although some of these questions have been broached using Sanger sequencing of VSG cDNA, technical limitations have prevented a high‐resolution, quantitative study of VSG expression during T. brucei infection. We have developed a method, termed VSG‐seq, for quantitatively examining the diversity of expressed VSGs in any population of trypanosomes. Based on de novo assembly, this approach can be used for the high‐resolution study of VSG expression in any strain of T. brucei, whether in the lab or in the field. Using VSG‐seq, we have studied the dynamics of VSG expression during chronic T . brucei infections in mice, and our experiments reveal more dynamic and nuanced host‐parasite interactions than previously expected. Nearly a quarter of the full‐length VSG repertoire is sampled within only four peaks of infection, and this level of diversity persists throughout infection. We can also detect the appearance and disappearance of mosaic VSGs using this method. Mosaic VSGs are novel variants which arise through recombination events within the parasite genome during infection, and our data hint at the mechanisms by which these mosaic VSGs form. We are now applying VSG‐seq to field isolates of T. brucei as well as to populations of parasites inhabiting extravascular spaces. Altogether, these results raise many new questions about the T. brucei host‐pathogen interaction; VSG‐seq will allow these questions to be addressed in their proper context, the natural host. Support or Funding Information This work has been supported in part by the NIH/National Institute of Allergy and Infectious Diseases (AI085973) to F.N.P., and by an NSF Graduate Research Fellowship (DGE‐1325261) to M.R.M.