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Withstanding the Challenges of Host Immunity: Antigenic Variation and the Trypanosome Surface Coat

  • James Peter John HallEmail author
  • Lindsey Plenderleith
Chapter

Abstract

Prolonged survival in the face of host immunity has been a major force shaping the biology and evolution of the African trypanosomes, and nowhere are the effects of this force more apparent than in the antigenic variation of the trypanosome variant surface glycoprotein (VSG) coat. The coat protects the trypanosome within it from immune effectors, and spontaneous and stochastic events occurring at the molecular level cause individual trypanosomes to change the VSG variant they are expressing. The consequence of this switching at the population level is a diverse population that can pre-empt the specific immune responses that arise against VSG. The template for changes to VSG is an extensive archive of silent VSG genes and pseudogenes. VSG from the archive are activated not only as full-length genes but also through the combination of segments to form mosaic VSG genes, a process that augments the potential for antigenic variation by introducing combinatorial variation and allowing VSG pseudogenes to be used. The main part of the archive occupies subtelomeres and so is itself prone to mutation and rapid evolution, which are important features when superinfection or reinfection of partially immune hosts is necessary. The antigenic variation ‘diversity phenotype’ is thus a multifaceted one, enlisting and coordinating fundamental mechanisms of cell biology to bring about a process that unfolds across populations, thereby facilitating the success of the African trypanosomes.

Keywords

Antigenic Variation Expression Site Monoallelic Expression Variant Surface Glycoprotein Trypanosome Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgement

This chapter is based on theses deposited at the University of Glasgow (J. P. J. Hall 2012; L. Plenderleith 2013). We would like to thank Dave Barry for his support, guidance and advice throughout our studies. This work was supported by the Wellcome Trust (Grant numbers 083224 and 086415). The Wellcome Trust Centre for Molecular Parasitology is supported by core funding from the Wellcome Trust (Grant number 085349).

References

  1. Aline RF, Stuart K (1989) Trypanosoma brucei: conserved sequence organization 3′ to telomeric variant surface glycoprotein genes. Exp Parasitol 68:57–66PubMedGoogle Scholar
  2. Allen G, Gurnett LP (1983) Locations of the six disulphide bonds in a variant surface glycoprotein (VSG 117) from Trypanosoma brucei. Biochem J 209:481–487PubMedGoogle Scholar
  3. Alsford S, duBois K, Horn D, Field MC (2012) Epigenetic mechanisms, nuclear architecture and the control of gene expression in trypanosomes. Expert Rev Mol Med 14:e13. doi: 10.1017/erm.2012.7 PubMedGoogle Scholar
  4. Amiguet-Vercher A, Pérez-Morga D, Pays A et al (2004) Loss of the mono-allelic control of the VSG expression sites during the development of Trypanosoma brucei in the bloodstream. Mol Microbiol 51:1577–1588. doi: 10.1111/j.1365-2958.2003.03937.x PubMedGoogle Scholar
  5. Askonas BA, Corsini AC, Clayton CE, Ogilvie BM (1979) Functional depletion of T- and B-memory cells and other lymphoid cell subpopulations-during trypanosomiasis. Immunology 36:313–321PubMedGoogle Scholar
  6. Aslett M, Aurrecoechea C, Berriman M et al (2010) TriTrypDB: a functional genomic resource for the Trypanosomatidae. Nucleic Acids Res 38:D457–D462. doi: 10.1093/nar/gkp851 PubMedGoogle Scholar
  7. Balmer O, Caccone A (2008) Multiple-strain infections of Trypanosoma brucei across Africa. Acta Trop 107:275–279. doi: 10.1016/j.actatropica.2008.06.006 PubMedGoogle Scholar
  8. Barbour AG, Dai Q, Restrepo BI et al (2006) Pathogen escape from host immunity by a genome program for antigenic variation. Proc Natl Acad Sci USA 103:18290–18295. doi: 10.1073/pnas.0605302103 PubMedGoogle Scholar
  9. Barnes RL, McCulloch R (2007) Trypanosoma brucei homologous recombination is dependent on substrate length and homology, though displays a differential dependence on mismatch repair as substrate length decreases. Nucleic Acids Res 35:3478–3493. doi: 10.1093/nar/gkm249 PubMedGoogle Scholar
  10. Barry JD (1986) Antigenic variation during Trypanosoma vivax infections of different host species. Parasitology 92(Pt 1):51–65PubMedGoogle Scholar
  11. Barry JD, McCulloch R (2001) Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Adv Parasitol 49:1–70PubMedGoogle Scholar
  12. Barry JD, Crowe JS, Vickerman K (1983) Instability of the Trypanosoma brucei rhodesiense metacyclic variable antigen repertoire. Nature 306:699–701PubMedGoogle Scholar
  13. Barry JD, Graham SV, Fotheringham M et al (1998) VSG gene control and infectivity strategy of metacyclic stage Trypanosoma brucei. Mol Biochem Parasitol 91:93–105PubMedGoogle Scholar
  14. Barry JD, Ginger ML, Burton P, McCulloch R (2003) Why are parasite contingency genes often associated with telomeres? Int J Parasitol 33:29–45PubMedGoogle Scholar
  15. Barry JD, Marcello L, Morrison LJ et al (2005) What the genome sequence is revealing about trypanosome antigenic variation. Biochem Soc Trans 33:986–989. doi: 10.1042/BST20050986 PubMedGoogle Scholar
  16. Barry JD, Hall JPJ, Plenderleith L (2012) Genome hyperevolution and the success of a parasite. Ann N Y Acad Sci 1267:11–17. doi: 10.1111/j.1749-6632.2012.06654.x PubMedGoogle Scholar
  17. Benmerzouga I, Concepción-Acevedo J, Kim H-S et al (2013) Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching. Mol Microbiol 87:196–210. doi: 10.1111/mmi.12093 PubMedGoogle Scholar
  18. Bernards A, Van der Ploeg LH, Frasch AC et al (1981) Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3′ end. Cell 27:497–505PubMedGoogle Scholar
  19. Bernards A, Van der Ploeg LH, Gibson WC et al (1986) Rapid change of the repertoire of variant surface glycoprotein genes in trypanosomes by gene duplication and deletion. J Mol Biol 190:1–10PubMedGoogle Scholar
  20. Berriman M, Ghedin E, Hertz-Fowler C et al (2005) The genome of the African trypanosome Trypanosoma brucei. Science 309:416–422. doi: 10.1126/science.1112642 PubMedGoogle Scholar
  21. Bitter W, Gerrits H, Kieft R, Borst P (1998) The role of transferrin-receptor variation in the host range of Trypanosoma brucei. Nature 391:499–502. doi: 10.1038/35166 PubMedGoogle Scholar
  22. Black SJ, Guirnalda P, Frenkel D et al (2010) Induction and regulation of Trypanosoma brucei VSG-specific antibody responses. Parasitology 137:2041–2049PubMedGoogle Scholar
  23. Blum ML, Down JA, Gurnett AM et al (1993) A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature 362:603–609. doi: 10.1038/362603a0 PubMedGoogle Scholar
  24. Boothroyd CE, Dreesen O, Leonova T et al (2009) A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei. Nature 459:278–281. doi: 10.1038/nature07982 PubMedGoogle Scholar
  25. Brown CA, Murray AW, Verstrepen KJ (2010) Rapid expansion and functional divergence of subtelomeric gene families in yeasts. Curr Biol 20:895–903. doi: 10.1016/j.cub.2010.04.027 PubMedGoogle Scholar
  26. Bussler H, Linder M, Linder D, Reinwald E (1998) Determination of the disulfide bonds within a B domain variant surface glycoprotein from Trypanosoma congolense. J Biol Chem 273:32582–32586PubMedGoogle Scholar
  27. Callejas S, Leech V, Reitter C, Melville S (2006) Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length. Genome Res 16:1109–1118. doi: 10.1101/gr.5147406 PubMedGoogle Scholar
  28. Campbell DA, van Bree MP, Boothroyd JC (1984) The 5′-limit of transposition and upstream barren region of a trypanosome VSG gene: tandem 76 base-pair repeats flanking (TAA)90. Nucleic Acids Res 12:2759–2774PubMedGoogle Scholar
  29. Caporale LH (2003) Natural selection and the emergence of a mutation phenotype: an update of the evolutionary synthesis considering mechanisms that affect genome variation. Annu Rev Microbiol 57:467–485. doi: 10.1146/annurev.micro.57.030502.090855 PubMedGoogle Scholar
  30. Carrington M, Miller N, Blum ML et al (1991) Variant specific glycoprotein of Trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues. J Mol Biol 221:823–835PubMedGoogle Scholar
  31. Caton AJ, Brownlee GG, Yewdell JW, Gerhard WU (1982) The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31:417–427PubMedGoogle Scholar
  32. Chamond N, Cosson A, Blom-Potar MC et al (2010) Trypanosoma vivax infections: pushing ahead with mouse models for the study of Nagana. I. Parasitological, hematological and pathological parameters. PLoS Negl Trop Dis 4:e792PubMedGoogle Scholar
  33. Chattopadhyay A, Jones NG, Nietlispach D et al (2005) Structure of the C-terminal domain from Trypanosoma brucei variant surface glycoprotein MITat1.2. J Biol Chem 280:7228–7235. doi: 10.1074/jbc.M410787200 PubMedGoogle Scholar
  34. Cohen C, Reinhardt B, Parry DA et al (1984) Alpha-helical coiled-coil structures of Trypanosoma brucei variable surface glycoproteins. Nature 311:169–171PubMedGoogle Scholar
  35. Conway C, Proudfoot C, Burton P et al (2002) Two pathways of homologous recombination in Trypanosoma brucei. Mol Microbiol 45:1687–1700PubMedGoogle Scholar
  36. Coustou V, Guegan F, Plazolles N, Baltz T (2010) Complete in vitro life cycle of Trypanosoma congolense: development of genetic tools. PLoS Negl Trop Dis 4:e618. doi: 10.1371/journal.pntd.0000618 PubMedGoogle Scholar
  37. Coutte L, Botkin DJ, Gao L, Norris SJ (2009) Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection. PLoS Pathog 5:e1000293. doi: 10.1371/journal.ppat.1000293 PubMedGoogle Scholar
  38. Cross GAM (1990) Cellular and genetic aspects of antigenic variation in trypanosomes. Annu Rev Immunol 8:83–110. doi: 10.1146/annurev.iy.08.040190.000503 PubMedGoogle Scholar
  39. Cully DF, Ip HS, Cross GA (1985) Coordinate transcription of variant surface glycoprotein genes and an expression site associated gene family in Trypanosoma brucei. Cell 42:173–182. doi: 10.1016/S0092-8674(85)80113-6 PubMedGoogle Scholar
  40. DuBois KN, Alsford S, Holden JM et al (2012) NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLoS Biol 10:e1001287. doi: 10.1371/journal.pbio.1001287 PubMedGoogle Scholar
  41. Duffy MF, Tham W-H (2007) Transcription and coregulation of multigene families in Plasmodium falciparum. Trends Parasitol 23:183–186. doi: 10.1016/j.pt.2007.02.010, discussion 186–7PubMedGoogle Scholar
  42. Engstler M, Pfohl T, Herminghaus S et al (2007) Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131:505–515. doi: 10.1016/j.cell.2007.08.046 PubMedGoogle Scholar
  43. Ferguson M (1991) Lipid anchors on membrane proteins. Curr Opin Struct Biol 1:522–529Google Scholar
  44. Ferguson MA, Duszenko M, Lamont GS et al (1986) Biosynthesis of Trypanosoma brucei variant surface glycoproteins. N-glycosylation and addition of a phosphatidylinositol membrane anchor. J Biol Chem 261:356–362PubMedGoogle Scholar
  45. Fernandez-Becerra C, Yamamoto MM, Vêncio RZN et al (2009) Plasmodium vivax and the importance of the subtelomeric multigene vir superfamily. Trends Parasitol 25:44–51. doi: 10.1016/j.pt.2008.09.012 PubMedGoogle Scholar
  46. Ferrante A, Allison AC (1983) Alternative pathway activation of complement by African trypanosomes lacking a glycoprotein coat. Parasite Immunol 5:491–498PubMedGoogle Scholar
  47. Field MC, Sergeenko T, Wang Y-N et al (2010) Chaperone requirements for biosynthesis of the trypanosome variant surface glycoprotein. PLoS One 5:e8468. doi: 10.1371/journal.pone.0008468 PubMedGoogle Scholar
  48. Figueiredo LM, Janzen CJ, Cross GAM (2008) A histone methyltransferase modulates antigenic variation in African trypanosomes. PLoS Biol 6:e161. doi: 10.1371/journal.pbio.0060161 PubMedGoogle Scholar
  49. Gardner MJ, Hall N, Fung E et al (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511. doi: 10.1038/nature01097 PubMedGoogle Scholar
  50. Gibson W, Bailey M (2003) The development of Trypanosoma brucei within the tsetse fly midgut observed using green fluorescent trypanosomes. Kinetoplastid Biol Dis 2:1PubMedGoogle Scholar
  51. Gjini E, Haydon DT, Barry JD, Cobbold CA (2010) Critical interplay between parasite differentiation, host immunity, and antigenic variation in trypanosome infections. Am Nat 176:424–439. doi: 10.1086/656276 PubMedGoogle Scholar
  52. Gjini E, Haydon DT, Barry JD, Cobbold CA (2012a) Linking the antigen archive structure to pathogen fitness in African trypanosomes. Proc Roy Soc B Biol Sci 280:20122129. doi: 10.1098/rspb.2012.2129 Google Scholar
  53. Gjini E, Haydon DT, Barry JD, Cobbold CA (2012b) The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes. Mol Biol Evol 29:3321–3331. doi: 10.1093/molbev/mss166 PubMedGoogle Scholar
  54. Graham SV, Barry JD (1995) Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei. Mol Cell Biol 15:5945–5956PubMedGoogle Scholar
  55. Graham VS, Barry JD (1996) Is point mutagenesis a mechanism for antigenic variation in Trypanosoma brucei? Mol Biochem Parasitol 79:35–45PubMedGoogle Scholar
  56. Greif G, de Leon MP, Lamolle G et al (2013) Transcriptome analysis of the bloodstream stage from the parasite Trypanosoma vivax. BMC Genomics 14:149. doi: 10.1186/1471-2164-14-149 PubMedGoogle Scholar
  57. Guirnalda P, Murphy NB, Nolan D, Black SJ (2007) Anti-Trypanosoma brucei activity in Cape buffalo serum during the cryptic phase of parasitemia is mediated by antibodies. Int J Parasitol 37:1391–1399. doi: 10.1016/j.ijpara.2007.04.019 PubMedGoogle Scholar
  58. Hall JPJ, Wang H, Barry JD (2013) Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation. PLoS Pathog 9(7): e1003502. doi:  10.1371/journal.ppat.1003502 PubMedGoogle Scholar
  59. Hernandez-Rivas R, Mattei D, Sterkers Y et al (1997) Expressed var genes are found in Plasmodium falciparum subtelomeric regions. Mol Cell Biol 17:604–611PubMedGoogle Scholar
  60. Hertz-Fowler C, Figueiredo LM, Quail MA et al (2008) Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS One 3:e3527. doi: 10.1371/journal.pone.0003527 PubMedGoogle Scholar
  61. Horn D, Barry JD (2005) The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes. Chromosome Res 13:525–533. doi: 10.1007/s10577-005-0991-8 PubMedGoogle Scholar
  62. Horn D, Cross GA (1997) Analysis of Trypanosoma brucei vsg expression site switching in vitro. Mol Biochem Parasitol 84:189–201PubMedGoogle Scholar
  63. Horn D, McCulloch R (2010) Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Curr Opin Microbiol 13:700–705. doi: 10.1016/j.mib.2010.08.009 PubMedGoogle Scholar
  64. Hudson RE, Aukema JE, Rispe C, Roze D (2002) Altruism, cheating, and anticheater adaptations in cellular slime molds. Am Nat 160:31–43. doi: 10.1086/340613 PubMedGoogle Scholar
  65. Hughes K, Wand M, Foulston L et al (2007) A novel ISWI is involved in VSG expression site downregulation in African trypanosomes. EMBO J 26:2400–2410. doi: 10.1038/sj.emboj.7601678 PubMedGoogle Scholar
  66. Hutchinson OC, Picozzi K, Jones NG et al (2007) Variant surface glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific. BMC Genomics 8:234. doi: 10.1186/1471-2164-8-234 PubMedGoogle Scholar
  67. Jackson DG, Owen MJ, Voorheis HP (1985) A new method for the rapid purification of both the membrane-bound and released forms of the variant surface glycoprotein from Trypanosoma brucei. Biochem J 230:195–202PubMedGoogle Scholar
  68. Jackson AP, Berry A, Aslett M et al (2012) Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species. Proc Natl Acad Sci USA 109:3416. doi: 10.1073/pnas.1117313109 PubMedGoogle Scholar
  69. Jones NG, Nietlispach D, Sharma R et al (2008) Structure of a glycosylphosphatidylinositol-anchored domain from a trypanosome variant surface glycoprotein. J Biol Chem 283:3584–3593. doi: 10.1074/jbc.M706207200 PubMedGoogle Scholar
  70. Kamper SM, Barbet AF (1992) Surface epitope variation via mosaic gene formation is potential key to long-term survival of Trypanosoma brucei. Mol Biochem Parasitol 53:33–44PubMedGoogle Scholar
  71. Kyes SA, Rowe JA, Kriek N, Newbold CI (1999) Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc Natl Acad Sci USA 96:9333–9338PubMedGoogle Scholar
  72. La Greca F, Magez S (2011) Vaccination against trypanosomiasis: can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist? Hum Vaccin 7:1225–1233. doi: 10.4161/hv.7.11.18203 PubMedGoogle Scholar
  73. Landeira D, Bart J-M, Van Tyne D, Navarro M (2009) Cohesin regulates VSG monoallelic expression in trypanosomes. J Cell Biol 186:243–254. doi: 10.1083/jcb.200902119 PubMedGoogle Scholar
  74. Laurent M, Pays E, Van der Werf A et al (1984) Translocation alters the activation rate of a trypanosome surface antigen gene. Nucleic Acids Res 12:8319–8328PubMedGoogle Scholar
  75. Lin Y, Hubert L, Wilson JH (2009) Transcription destabilizes triplet repeats. Mol Carcinog 48:350–361. doi: 10.1002/mc.20488 PubMedGoogle Scholar
  76. Linardopoulou EV, Williams EM, Fan Y et al (2005) Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature 437:94–100. doi: 10.1038/nature04029 PubMedGoogle Scholar
  77. Liu AY, Van der Ploeg LH, Rijsewijk FA, Borst P (1983) The transposition unit of variant surface glycoprotein gene 118 of Trypanosoma brucei. Presence of repeated elements at its border and absence of promoter-associated sequences. J Mol Biol 167:57–75PubMedGoogle Scholar
  78. Liu AY, Michels PA, Bernards A, Borst P (1985) Trypanosome variant surface glycoprotein genes expressed early in infection. J Mol Biol 182:383–396PubMedGoogle Scholar
  79. Lythgoe KA, Morrison LJ, Read AF, Barry JD (2007) Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation. Proc Natl Acad Sci USA 104:8095–8100. doi: 10.1073/pnas.0606206104 PubMedGoogle Scholar
  80. MacGregor P, Matthews KR (2012) Identification of the regulatory elements controlling the transmission stage-specific gene expression of PAD1 in Trypanosoma brucei. Nucleic Acids Res 40:7705–7717. doi: 10.1093/nar/gks533 PubMedGoogle Scholar
  81. MacGregor P, Savill NJ, Hall D, Matthews KR (2011) Transmission stages dominate trypanosome within-host dynamics during chronic infections. Cell Host Microbe 9:310–318. doi: 10.1016/j.chom.2011.03.013 PubMedGoogle Scholar
  82. MacGregor P, Szöőr B, Savill NJ, Matthews KR (2012) Trypanosomal immune evasion, chronicity and transmission: an elegant balancing act. Nat Rev Microbiol 10(6):431–438. doi: 10.1038/nrmicro2779 PubMedGoogle Scholar
  83. Macleod A, Tait A, Turner CM (2001) The population genetics of Trypanosoma brucei and the origin of human infectivity. Philos Trans R Soc Lond B Biol Sci 356:1035–1044. doi: 10.1098/rstb.2001.0892 PubMedGoogle Scholar
  84. Magez S, Schwegmann A, Atkinson R et al (2008) The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice. PLoS Pathog 4:e1000122. doi: 10.1371/journal.ppat.1000122 PubMedGoogle Scholar
  85. Marcello L, Barry JD (2007a) 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 17:1344–1352. doi: 10.1101/gr.6421207 PubMedGoogle Scholar
  86. Marcello L, Barry JD (2007b) From silent genes to noisy populations-dialogue between the genotype and phenotypes of antigenic variation. J Eukaryot Microbiol 54:14–17. doi: 10.1111/j.1550-7408.2006.00227.x PubMedGoogle Scholar
  87. Martinsohn JT, Sousa AB, Guethlein LA, Howard JC (1999) The gene conversion hypothesis of MHC evolution: a review. Immunogenetics 50:168–200PubMedGoogle Scholar
  88. McConnell J, Gurnett AM, Cordingley JS et al (1981) Biosynthesis of Trypanosoma brucei variant surface glycoprotein. I. Synthesis, size, and processing of an N-terminal signal peptide. Mol Biochem Parasitol 4:225–242PubMedGoogle Scholar
  89. McCulloch R, Barry JD (1999) A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation. Genes Dev 13:2875–2888PubMedGoogle Scholar
  90. McCulloch R, Horn D (2009) What has DNA sequencing revealed about the VSG expression sites of African trypanosomes? Trends Parasitol 25:359–363. doi: 10.1016/j.pt.2009.05.007 PubMedGoogle Scholar
  91. Mefford HC, Trask BJ (2002) The complex structure and dynamic evolution of human subtelomeres. Nat Rev Genet 3:91–102. doi: 10.1038/nrg727 PubMedGoogle Scholar
  92. Mehlert A, Bond CS, Ferguson MAJ (2002) The glycoforms of a Trypanosoma brucei variant surface glycoprotein and molecular modeling of a glycosylated surface coat. Glycobiology 12:607–612PubMedGoogle Scholar
  93. Melville SE, Leech V, Navarro M, Cross GA (2000) The molecular karyotype of the megabase chromosomes of Trypanosoma brucei stock 427. Mol Biochem Parasitol 111:261–273PubMedGoogle Scholar
  94. Michels PA, Liu AY, Bernards A et al (1983) Activation of the genes for variant surface glycoproteins 117 and 118 in Trypanosoma brucei. J Mol Biol 166:537–556PubMedGoogle Scholar
  95. Moraes Barros RR, Marini MM, Antônio CR et al (2012) Anatomy and evolution of telomeric and subtelomeric regions in the human protozoan parasite Trypanosoma cruzi. BMC Genomics 13:229. doi: 10.1186/1471-2164-13-229 PubMedGoogle Scholar
  96. Morrison WI, Black SJ, Paris J et al (1982) Protective immunity and specificity of antibody responses elicited in cattle by irradiated Trypanosoma brucei. Parasite Immunol 4:395–407PubMedGoogle Scholar
  97. Morrison LJ, Majiwa P, Read AF, Barry JD (2005) Probabilistic order in antigenic variation of Trypanosoma brucei. Int J Parasitol 35:961–972. doi: 10.1016/j.ijpara.2005.05.004 PubMedGoogle Scholar
  98. Morrison LJ, Marcello L, McCulloch R (2009) Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity. Cell Microbiol 11:1724–1734. doi: 10.1111/j.1462-5822.2009.01383.x PubMedGoogle Scholar
  99. Mosser DM, Roberts JF (1982) Trypanosoma brucei: recognition in vitro of two developmental forms by murine macrophages. Exp Parasitol 54:310–316PubMedGoogle Scholar
  100. Muñoz-Jordán JL, Davies KP, Cross GAM (1996) Stable expression of mosaic coats of variant surface glycoproteins in Trypanosoma brucei. Science 272:1795–1797PubMedGoogle Scholar
  101. Navarro M, Gull K (2001) A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature 414:759–763. doi: 10.1038/414759a PubMedGoogle Scholar
  102. Navarro M, Peñate X, Landeira D (2007) Nuclear architecture underlying gene expression in Trypanosoma brucei. Trends Microbiol 15:263–270. doi: 10.1016/j.tim.2007.04.004 PubMedGoogle Scholar
  103. Nei M, Rooney AP (2005) Concerted and birth-and-death evolution of multigene families. Annu Rev Genet 39:121–152. doi: 10.1146/annurev.genet.39.073003.112240 PubMedGoogle Scholar
  104. Njiokou F, Laveissière C, Simo G et al (2006) Wild fauna as a probable animal reservoir for Trypanosoma brucei gambiense in Cameroon. Infect Genet Evol 6:147–153. doi: 10.1016/j.meegid.2005.04.003 PubMedGoogle Scholar
  105. O’Beirne C, Lowry CM, Voorheis HP (1998) Both IgM and IgG anti-VSG antibodies initiate a cycle of aggregation-disaggregation of bloodstream forms of Trypanosoma brucei without damage to the parasite. Mol Biochem Parasitol 91:165–193PubMedGoogle Scholar
  106. Oberle M, Balmer O, Brun R, Roditi I (2010) Bottlenecks and the maintenance of minor genotypes during the life cycle of Trypanosoma brucei. PLoS Pathog 6:e1001023. doi: 10.1371/journal.ppat.1001023 PubMedGoogle Scholar
  107. Overath P, Chaudhri M, Steverding D, Ziegelbauer K (1994) Invariant surface proteins in bloodstream forms of Trypanosoma brucei. Parasitol Today (Regul Ed) 10:53–58Google Scholar
  108. Overath P, Stierhof YD, Wiese M (1997) Endocytosis and secretion in trypanosomatid parasites – Tumultuous traffic in a pocket. Trends Cell Biol 7:27–33. doi: 10.1016/S0962-8924(97)10046-0 PubMedGoogle Scholar
  109. Pal A, Hall BS, Jeffries TR, Field MC (2003) Rab5 and Rab11 mediate transferrin and anti-variant surface glycoprotein antibody recycling in Trypanosoma brucei. Biochem J 374:443–451. doi: 10.1042/BJ20030469 PubMedGoogle Scholar
  110. Pan W, Ogunremi O, Wei G et al (2006) CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: diverse effect on subsequent synthesis of tumor necrosis factor alpha and nitric oxide. Microbes Infect 8:1209–1218. doi: 10.1016/j.micinf.2005.11.009 PubMedGoogle Scholar
  111. Parsons M, Nelson RG, Watkins KP, Agabian N (1984) Trypanosome mRNAs share a common 5′ spliced leader sequence. Cell 38:309–316PubMedGoogle Scholar
  112. Pays E, Lheureux M, Steinert M (1981) Analysis of the DNA and RNA changes associated with the expression of isotypic variant-specific antigens of trypanosomes. Nucleic Acids Res 9:4225–4238PubMedGoogle Scholar
  113. Pays E, Guyaux M, Aerts D et al (1985) Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes. Nature 316:562–564PubMedGoogle Scholar
  114. Povelones ML, Gluenz E, Dembek M et al (2012) Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei. PLoS Pathog 8:e1003010. doi: 10.1371/journal.ppat.1003010 PubMedGoogle Scholar
  115. Radwanska M, Guirnalda P, De Trez C et al (2008) Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses. PLoS Pathog 4:e1000078. doi: 10.1371/journal.ppat.1000078 PubMedGoogle Scholar
  116. Recker M, Buckee CO, Serazin A et al (2011) Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern. PLoS Pathog 7:e1001306. doi: 10.1371/journal.ppat.1001306 PubMedGoogle Scholar
  117. Reece SE, Pollitt LC, Colegrave N, Gardner A (2011) The meaning of death: evolution and ecology of apoptosis in protozoan parasites. PLoS Pathog 7:e1002320. doi: 10.1371/journal.ppat.1002320 PubMedGoogle Scholar
  118. Riethman H, Ambrosini A, Paul S (2005) Human subtelomere structure and variation. Chromosome Res 13:505–515. doi: 10.1007/s10577-005-0998-1 PubMedGoogle Scholar
  119. Rivero FD, Saura A, Prucca CG et al (2010) Disruption of antigenic variation is crucial for effective parasite vaccine. Nat Med 16:551–557. doi: 10.1038/nm.2141, 1p following 557PubMedGoogle Scholar
  120. Robinson NP, Burman N, Melville SE, Barry JD (1999) Predominance of duplicative VSG gene conversion in antigenic variation in African trypanosomes. Mol Cell Biol 19:5839–5846PubMedGoogle Scholar
  121. Rogers MB, Hilley JD, Dickens NJ et al (2011) Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Genome Res 21:2129–2142. doi: 10.1101/gr.122945.111 PubMedGoogle Scholar
  122. Roth CW, Bringaud F, Layden RE et al (1989) Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes. Proc Natl Acad Sci USA 86:9375–9379PubMedGoogle Scholar
  123. Salmon D, Vanwalleghem G, Morias Y et al (2012) Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host. Science 337:463–466. doi: 10.1126/science.1222753 PubMedGoogle Scholar
  124. Scherf A, Lopez-Rubio JJ, Riviere L (2008) Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol 62:445–470. doi: 10.1146/annurev.micro.61.080706.093134 PubMedGoogle Scholar
  125. Schwede A, Jones N, Engstler M, Carrington M (2011) The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes. Mol Biochem Parasitol 175:201–204. doi: 10.1016/j.molbiopara.2010.11.004 PubMedGoogle Scholar
  126. Seed JR, Sechelski J (1988) Growth of pleomorphic Trypanosoma brucei rhodesiense in irradiated inbred mice. J Parasitol 74:781–789PubMedGoogle Scholar
  127. Seed JR, Seed JR, Wenck MA, Wenck MA (2003) Role of the long slender to short stumpy transition in the life cycle of the African trypanosomes. Kinetoplastid Biol Dis 2:3. doi: 10.1186/1475-9292-2-3 PubMedGoogle Scholar
  128. Seyfang A, Mecke D, Duszenko M (1990) Degradation, recycling, and shedding of Trypanosoma brucei variant surface glycoprotein. J Protozool 37:546–552PubMedGoogle Scholar
  129. Smith TK, Vasileva N, Gluenz E et al (2009) Blocking variant surface glycoprotein synthesis in Trypanosoma brucei triggers a general arrest in translation initiation. PLoS One 4:e7532. doi: 10.1371/journal.pone.0007532 PubMedGoogle Scholar
  130. Stanne TM, Rudenko G (2010) Active VSG expression sites in Trypanosoma brucei are depleted of nucleosomes. Eukaryot Cell 9:136–147. doi: 10.1128/EC.00281-09 PubMedGoogle Scholar
  131. Stringer JR, Keely SP (2001) Genetics of surface antigen expression in Pneumocystis carinii. Infect Immun 69:627–639. doi: 10.1128/IAI.69.2.627-639.2001 PubMedGoogle Scholar
  132. Taylor JE, Rudenko G (2006) Switching trypanosome coats: what’s in the wardrobe? Trends Genet 22:614–620. doi: 10.1016/j.tig.2006.08.003 PubMedGoogle Scholar
  133. Thon G, Baltz T, Giroud C, Eisen H (1990) Trypanosome variable surface glycoproteins: composite genes and order of expression. Genes Dev 4:1374–1383PubMedGoogle Scholar
  134. Tiengwe C, Marcello L, Farr H et al (2012) Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. Cell Rep 2:185–197. doi: 10.1016/j.celrep.2012.06.007 PubMedGoogle Scholar
  135. Timmers HT, De Lange T, Kooter JM, Borst P (1987) Coincident multiple activations of the same surface antigen gene in Trypanosoma brucei. J Mol Biol 194:81–90PubMedGoogle Scholar
  136. Turner CMR (1997) The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei. FEMS Microbiol Lett 153:227–231PubMedGoogle Scholar
  137. Turner CMR (1999) Antigenic variation in Trypanosoma brucei infections: an holistic view. J Cell Sci 112(Pt 19):3187–3192PubMedGoogle Scholar
  138. Turner C, Barry J (1989) High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Parasitology 99:67–75PubMedGoogle Scholar
  139. Turner CM, Barry JD, Maudlin I, Vickerman K (1988) An estimate of the size of the metacyclic variable antigen repertoire of Trypanosoma brucei rhodesiense. Parasitology 97(Pt 2):269–276PubMedGoogle Scholar
  140. Turner CM, Aslam N, Dye C (1995) Replication, differentiation, growth and the virulence of Trypanosoma brucei infections. Parasitology 111(Pt 3):289–300PubMedGoogle Scholar
  141. Ulbert S, Chaves I, Borst P (2002) Expression site activation in Trypanosoma brucei with three marked variant surface glycoprotein gene expression sites. Mol Biochem Parasitol 120:225–235PubMedGoogle Scholar
  142. Van Den Abbeele J, Claes Y, van Bockstaele D et al (1999) Trypanosoma brucei spp. development in the tsetse fly: characterization of the post-mesocyclic stages in the foregut and proboscis. Parasitology 118(Pt 5):469–478Google Scholar
  143. Van der Ploeg LH, Cornelissen AW, Barry JD, Borst P (1984) Chromosomes of kinetoplastida. EMBO J 3:3109–3115PubMedGoogle Scholar
  144. Van Meirvenne N, Magnus E, Buscher P (1995) Evaluation of variant specific trypanolysis tests for serodiagnosis of human infections with Trypanosoma brucei gambiense. Acta Trop 60:189–199PubMedGoogle Scholar
  145. Vassella E, Reuner B, Yutzy B, Boshart M (1997) Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway. J Cell Sci 110(Pt 21):2661–2671PubMedGoogle Scholar
  146. Vickerman K (1969) On the surface coat and flagellar adhesion in trypanosomes. J Cell Sci 5:163–193PubMedGoogle Scholar
  147. Wang Q-P, Kawahara T, Horn D (2010) Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes. Mol Microbiol 77:1237–1245. doi: 10.1111/j.1365-2958.2010.07284.x PubMedGoogle Scholar
  148. Weiden M, Osheim YN, Beyer AL, Van der Ploeg LH (1991) Chromosome structure: DNA nucleotide sequence elements of a subset of the minichromosomes of the protozoan Trypanosoma brucei. Mol Cell Biol 11:3823–3834PubMedGoogle Scholar
  149. West SA, Griffin AS, Gardner A, Diggle SP (2006) Social evolution theory for microorganisms. Nat Rev Microbiol 4:597–607. doi: 10.1038/nrmicro1461 PubMedGoogle Scholar
  150. Wickstead B, Ersfeld K, Gull K (2004) The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes. Genome Res 14:1014–1024. doi: 10.1101/gr.2227704 PubMedGoogle Scholar
  151. Young R, Taylor JE, Kurioka A et al (2008) Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum. BMC Genomics 9:385PubMedGoogle Scholar
  152. Zhuang Y, Futse JE, Brown WC et al (2007) Maintenance of antibody to pathogen epitopes generated by segmental gene conversion is highly dynamic during long-term persistent infection. Infect Immun 75:5185–5190. doi: 10.1128/IAI.00913-07 PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • James Peter John Hall
    • 1
    • 2
    Email author
  • Lindsey Plenderleith
    • 1
    • 3
  1. 1.Wellcome Trust Centre for Molecular ParasitologyUniversity of GlasgowGlasgowUK
  2. 2.Department of BiologyUniversity of YorkYorkUK
  3. 3.Institute of Evolutionary BiologyUniversity of EdinburghEdinburghUK

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