TY - JOUR
T1 - Variant antigen diversity in Trypanosoma vivax is not driven by recombination
AU - Pereira, Sara Silva
AU - de Almeida Castilho Neto, Kayo J.G.
AU - Duffy, Craig W.
AU - Richards, Peter
AU - Noyes, Harry
AU - Ogugo, Moses
AU - Rogério André, Marcos
AU - Bengaly, Zakaria
AU - Kemp, Steve
AU - Teixeira, Marta M.G.
AU - Machado, Rosangela Z.
AU - Jackson, Andrew P.
N1 - Funding Information:
This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/M022811/1 and BB/R021139/1), an International Veterinary Vaccinology Network (IVVN) pump-priming award, a Bill and Melinda Gates Foundation Grand Challenges Explorations award (Round 11), and the Wellcome Trust (WT206815/Z/17/Z).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - African trypanosomes (Trypanosoma) are vector-borne haemoparasites that survive in the vertebrate bloodstream through antigenic variation of their Variant Surface Glycoprotein (VSG). Recombination, or rather segmented gene conversion, is fundamental in Trypanosoma brucei for both VSG gene switching and for generating antigenic diversity during infections. Trypanosoma vivax is a related, livestock pathogen whose VSG lack structures that facilitate gene conversion in T. brucei and mechanisms underlying its antigenic diversity are poorly understood. Here we show that species-wide VSG repertoire is broadly conserved across diverse T. vivax clinical strains and has limited antigenic repertoire. We use variant antigen profiling, coalescent approaches and experimental infections to show that recombination plays little role in diversifying T. vivax VSG sequences. These results have immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission, requiring reconsideration of the wider epidemiology of animal African trypanosomiasis.
AB - African trypanosomes (Trypanosoma) are vector-borne haemoparasites that survive in the vertebrate bloodstream through antigenic variation of their Variant Surface Glycoprotein (VSG). Recombination, or rather segmented gene conversion, is fundamental in Trypanosoma brucei for both VSG gene switching and for generating antigenic diversity during infections. Trypanosoma vivax is a related, livestock pathogen whose VSG lack structures that facilitate gene conversion in T. brucei and mechanisms underlying its antigenic diversity are poorly understood. Here we show that species-wide VSG repertoire is broadly conserved across diverse T. vivax clinical strains and has limited antigenic repertoire. We use variant antigen profiling, coalescent approaches and experimental infections to show that recombination plays little role in diversifying T. vivax VSG sequences. These results have immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission, requiring reconsideration of the wider epidemiology of animal African trypanosomiasis.
KW - Antigenic Variation/genetics
KW - DNA, Protozoan
KW - Evolution, Molecular
KW - Genome, Protozoan
KW - Host-Parasite Interactions/immunology
KW - Immune evasion
KW - Phylogeny
KW - Protozoan Proteins/genetics
KW - Recombination, Genetic/genetics
KW - Sequence homology
KW - Species specificity
KW - Transcriptome
KW - Trypanosoma brucei brucei/genetics
KW - Trypanosoma vivax/genetics
KW - Trypanosomiasis, African/immunology
KW - Variant Surface Glycoproteins, Trypanosoma/genetics
UR - http://www.scopus.com/inward/record.url?scp=85079336540&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-14575-8
DO - 10.1038/s41467-020-14575-8
M3 - Article
C2 - 32051413
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 844
ER -