Quantitative sequencing confirms VSG diversity as central to immune evasion by Trypanosoma brucei.

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.

McCulloch R ，Field MC 《-》

Variant antigen diversity in Trypanosoma vivax is not driven by recombination.

Silva Pereira S ，de Almeida Castilho Neto KJG ，Duffy CW ，Richards P ，Noyes H ，Ogugo M ，Rogério André M ，Bengaly Z ，Kemp S ，Teixeira MMG ，Machado RZ ，Jackson AP ... -  《Nature Communications》

African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system.

Trypanosoma brucei parasites successfully evade the host immune system by periodically switching the dense coat of variant surface glycoprotein (VSG) at the cell surface. Each parasite expresses VSGs in a monoallelic fashion that is tightly regulated. The consequences of exposing multiple VSGs during an infection, in terms of antibody response and disease severity, remain unknown. In this study, we overexpressed a high-mobility group box protein, TDP1, which was sufficient to open the chromatin of silent VSG expression sites, to disrupt VSG monoallelic expression, and to generate viable and healthy parasites with a mixed VSG coat. Mice infected with these parasites mounted a multi-VSG antibody response, which rapidly reduced parasitemia. Consequently, we observed prolonged survival in which nearly 90% of the mice survived a 30-d period of infection with undetectable parasitemia. Immunodeficient RAG2 knock-out mice were unable to control infection with TDP1-overexpressing parasites, showing that the adaptive immune response is critical to reducing disease severity. This study shows that simultaneous exposure of multiple VSGs is highly detrimental to the parasite, even at the very early stages of infection, suggesting that drugs that disrupt VSG monoallelic expression could be used to treat trypanosomiasis.

Aresta-Branco F ，Sanches-Vaz M ，Bento F ，Rodrigues JA ，Figueiredo LM ... -  《-》

Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species.

Jackson AP ，Berry A ，Aslett M ，Allison HC ，Burton P ，Vavrova-Anderson J ，Brown R ，Browne H ，Corton N ，Hauser H ，Gamble J ，Gilderthorp R ，Marcello L ，McQuillan J ，Otto TD ，Quail MA ，Sanders MJ ，van Tonder A ，Ginger ML ，Field MC ，Barry JD ，Hertz-Fowler C ，Berriman M ... -  《-》

Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation.

Pinger J ，Chowdhury S ，Papavasiliou FN 《Nature Communications》