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The in vivo dynamics of antigenic variation in Trypanosoma brucei

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Science  27 Mar 2015:
Vol. 347, Issue 6229, pp. 1470-1473
DOI: 10.1126/science.aaa4502

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Trypanosomes reveal tricky tricks in vivo

The sleeping sickness parasite, Trypanosoma brucei, is covered with variant surface glyco proteins (VSGs) recognized by the host's immune system. The parasite uses a repertoire of 2000 VSG genes to switch between different surface variants, continually evading the host's defensive responses. Classic experiments showed that one variant succeeded another, causing waves of infection; however, infection in animals shows different behavior. Mugnier et al. discovered that several VSGs are expressed simultaneously and that the repertoire for variation is amplified even more by recombination between the genes to make mosaic VSGs.

Science, this issue p. 1470

Abstract

Trypanosoma brucei, a causative agent of African Sleeping Sickness, constantly changes its dense variant surface glycoprotein (VSG) coat to avoid elimination by the immune system of its mammalian host, using an extensive repertoire of dedicated genes. However, the dynamics of VSG expression in T. brucei during an infection are poorly understood. We have developed a method, based on de novo assembly of VSGs, for quantitatively examining the diversity of expressed VSGs in any population of trypanosomes and monitored VSG population dynamics in vivo. Our experiments revealed unexpected diversity within parasite populations and a mechanism for diversifying the genome-encoded VSG repertoire. The interaction between T. brucei and its host is substantially more dynamic and nuanced than previously expected.

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