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Chapter 21 : Molecular Aspects of Antigenic Variation in

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Abstract:

Antigenic variation is a key survival strategy employed by a wide range of infectious organisms, allowing them to colonize and persist in a vertebrate host in the face of an evolving immune response. Variant surface antigens (VSA) of the parasite responsible for the most severe form of human malaria, , also contribute significantly to the pathology of disease. Characterization of gene coding sequences is difficult due to their extreme diversity, but there are certain key conserved features in gene structure. The conservation in upstream sequences, in terms of both sequence and organization, may indicate some evolutionary pressure that restricts recombination between limited subsets of genes. The adhesion of different Duffy-binding-like (DBL) and cysteine-rich interdomain region (CIDR) domain types to host cell-surface molecules has been investigated in heterologous expression studies, establishing domains responsible for particular adhesive phenotypes and pinpointing regions critical for binding. Clonal switching of gene expression during chronic infection reflects the sum of several molecular processes, including temporal regulation of gene expression during intraerythrocytic development, mutually exclusive expression of only one variant per infected erythrocytes (IE), and the ability to switch expression in progeny parasites. Chronic infection with malaria is characterized by periodic peaks of parasitemia. A consensus model for variant expression during chronic infections can now be proposed. Following merozoite release from the liver, an initial erythrocyte membrane protein 1 (PfEMP1) variant dominates the first cycle of intraerythrocytic infection.

Citation: Horrocks P, Kyes S, Bull P, Deitsch K. 2005. Molecular Aspects of Antigenic Variation in , p 399-415. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch21

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FIGURE 1

(A) Chromosomal distribution and orientation of the multigene family. genes are indicated as block arrows with the upstream sequence type () indicated using letters A, B, and C. The most common subtelomeric organization of genes is an gene in tail-to-tail orientation with a gene immediately adjacent to the telomere-associated repeat sequences (TARES). Additional features which may or may not be present are shown in brackets. Some subtelomeric regions contain an gene and/or other members of the () and () multigene families. D and genes are always in the same relative location and/or orientation as -type genes. When present, chromosome-central gene variants are either or type and are typically clustered in a head-to-tail orientation. The CD36-binding phenotype of the encoded PfEMP1 appears to be predictable from gene location, as demonstrated in heterologous protein expression studies ( ). CSA binding is likely to be mediated by the -type -encoded PfEMP1 ( ). genes encoding PfEMP1 for other severe disease phenotypes, such as ICAM-1 binding and CR1-mediated rosetting, have been confirmed with isolate IT/FCR3 but not with the genome project isolate 3D7. These genes are type , (ICAM-1) ( ) and (CR1) ( ). (B) gene structure and sequence features. The basic coding sequence units of a gene include an N-terminal sequence (NTS), at least two DBL domains, and the transmembrane (TM) region with exon 2 encoding the semiconserved acidic terminal sequence (ATS). Noncoding features include the relatively conserved 5′ region (), the intron, and the 3′ region (). A common polymorphic gene is depicted, indicating the formation of the NTS, first DBLα and then CIDR, into what is termed the head structure. The presence of CIDR1α in the head structure predicts that the encoded PfEMP1 binds to CD36. Other domains that may be present in the PfEMP1 molecule are indicated below the basic PfEMP1 organization. Adhesion by these domains to certain host ligands, e.g., DBL1α1 to CR1, DBLβC2 to ICAM-1, and DBLγ to CSA ( ), has been reported, although the presence of these domains in the encoded PfEMP1 molecule should not always be assumed to indicate a particular adhesive property of the IE.

Citation: Horrocks P, Kyes S, Bull P, Deitsch K. 2005. Molecular Aspects of Antigenic Variation in , p 399-415. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch21
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Image of FIGURE 2
FIGURE 2

Control of gene expression. The control of gene expression is complex and includes temporal regulation during a cell cycle, mutually exclusive expression of a single variant in an IE, as well as switching of variants expressed in progeny clones. The status of expression for 5 of the 60 genes present per haploid genome is represented in the ring and pigmented trophozoite stages during two cell cycles. Changes to the IE surface are indicated schematically, from smooth (rings) to patterned (pigmented trophozoites), emphasizing that PfEMP1 absent from the IE surface for most of the ring stage is present during trophozoite stages. In the first cell cycle, variant 1 encodes a PfEMP1 variant (light grey dots) on the trophozoite surface, whereas in the second cycle a switch to a variant (dark grey dots) encoded by variant 2 has occurred. During the ring stage of cell cycle 1, variant 1 is exclusively transcribed, giving rise to the corresponding PfEMP1 variant on the trophozoite IE surface while the remainder of the repertoire is transcriptionally silent (at least in terms of mRNA that encodes surface exposed PfEMP1). In trophozoite stage IE, all gene variants are silenced (note transcription from the intronic promoter, although possibly not from that of variant 1) except for one variant (here variant 60, analogous to the conserved ).Thus genes are subject to both temporal and mutually exclusive transcriptional regulation within a cell cycle. During an infection a small proportion of the parasite population may switch expression of PfEMP1. This is represented here by a switch to expression of the PfEMP1 variant 2 in cell cycle 2. variant 2 is subject to the same temporal and mutually exclusive transcriptional regulation as variant 1 during cell cycle 1.

Citation: Horrocks P, Kyes S, Bull P, Deitsch K. 2005. Molecular Aspects of Antigenic Variation in , p 399-415. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch21
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Image of FIGURE 3
FIGURE 3

Do genes exist in three transcriptional states? One interpretation of switching rates measured in vitro was that each gene is capable of existing in one of three transcriptional states. First, the on state is where a gene is transcribed and encodes the PfEMP1 molecule on the IE surface. Second, the gene is transcriptionally silent, off but capable of being activated. Transition rates between these two transcriptional states (solid arrows) have been measured and shown to be an intrinsic property of each gene variant. A third transcriptional state was suggested from in vitro data, indicating that the variant expression history impacts on the ability of a gene variant to be switched on. This is termed the heavily silenced transcriptional state. How genes transition to and from this state, and the rates at which this occurs, is not known (broken arrows); their speculative nature is emphasized here by their separation in a second (lower) grey box. Thus, it is proposed that the overall transcriptional status of a gene variant is dependent not only on the intrinsic switch rate between on and off states, but also on whether the gene exists in the heavily silenced state.

Citation: Horrocks P, Kyes S, Bull P, Deitsch K. 2005. Molecular Aspects of Antigenic Variation in , p 399-415. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch21
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References

/content/book/10.1128/9781555817558.chap21
1. Agur, Z.,, D. Abiri,, and L. H. Van der Ploeg. 1989. Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates. Proc. Natl. Acad. Sci. USA 86:96269630.
2. Akhtar, A. 2003. Dosage compensation: an intertwined world of RNA and chromatin remodelling. Curr. Opin. Genet. Dev. 13:161169.
3. Aravind, L.,, L. M. Iyer,, T. E. Wellems,, and L. H. Miller. 2003. Plasmodium biology: genomic gleanings. Cell 115:771785.
4. Bahl, A.,, B. Brunk,, J. Crabtree,, M. J. Fraunholz,, B. Gajria,, G. R. Grant,, H. Ginsburg,, D. Gupta,, J. C. Kissinger,, P. Labo,, L. Li,, M. D. Mailman,, A. J. Milgram,, D. S. Pearson,, D. S. Roos,, J. Schug,, C. J. Stoeckert, Jr.,, and P. Whetzel. 2003. PlasmoDB: the Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Res. 31:212215.
5. Baruch, D. I.,, X. C. Ma,, H. B. Singh,, X. Bi,, B. L. Pasloske,, and R. J. Howard. 1997. Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence. Blood 90:37663775.
6. Baruch, D. I.,, B. L. Pasloske,, H. B. Singh,, X. Bi,, X. C. Ma,, M. Feldman,, T. F. Taraschi,, and R. J. Howard. 1995. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82:7787.
7. Borst, P. 2002. Antigenic variation and allelic exclusion. Cell 109:58.
8. Borst, P.,, W. Bitter,, R. McCulloch,, F. Van Leeuwen,, and G. Rudenko. 1995. Antigenic variation in malaria. Cell 82:14.
9. Borst, P.,, G. Rudenko,, P. A. Blundell,, F. van Leeuwen,, M.A. Cross,, R. McCulloch,, H. Gerrits,, and I. M. Chaves. 1997. Mechanisms of antigenic variation in African trypanosomes. Behring Inst. Mitt. March:115.
10. Borst, P.,, and S. Ulbert. 2001. Control of VSG gene expression sites. Mol. Biochem. Parasitol. 114:1727.
11. Brannan, L. R.,, S. A. McLean,, and R. S. Phillips. 1993. Antigenic variants of Plasmodium chabaudi chabaudi AS and the effects of mosquito transmission. Parasite Immunol. 15:135141.
12. Brannan, L. R.,, C. M. Turner,, and R. S. Phillips. 1994. Malaria parasites undergo antigenic variation at high rates in vivo. Proc. R. Soc. Lond. B Biol. Sci. 256:7175.
13. Buffet, P. A.,, B. Gamain,, C. Scheidig,, D. Baruch,, J. D. Smith,, R. Hernandez-Rivas,, B. Pouvelle,, S. Oishi,, N. Fujii,, T. Fusai,, D. Parzy,, L. H. Miller,, J. Gysin,, and A. Scherf. 1999. Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection. Proc. Natl. Acad. Sci. USA 96:1274312748.
14. Bull, P. C.,, M. Kortok,, O. Kai,, F. Ndungu,, A. Ross,, B. S. Lowe,, C. I. Newbold,, and K. Marsh. 2000. Plasmodium falciparum-infected erythrocytes: agglutination by diverse Kenyan plasma is associated with severe disease and young host age. J. Infect. Dis. 182:252259.
15. Bull, P. C.,, B. S. Lowe,, N. Kaleli,, F. Njuga,, M. Kortok,, A. Ross,, F. Ndungu,, R.W. Snow,, and K. Marsh. 2002. Plasmodium falciparum infections are associated with agglutinating antibodies to parasite-infected erythrocyte surface antigens among healthy Kenyan children. J. Infect. Dis. 185:16881691.
16. Bull, P.C.,, B. S. Lowe,, M. Kortok,, C. S. Molyneux,, C. I. Newbold,, and K. Marsh. 1998. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat. Med. 4:358360.
17. Bull, P. C.,, A. Pain,, F. M. Ndungu,, S. M. Kinyanjui,, D. J. Roberts,, C. I. Newbold,, and K. Marsh. Plasmodium falciparum antigenic variation: relationships between in-vivo selection, the acquired antibody response and disease severity. J. Infect. Dis., in press.
18. Calderwood, M. S.,, L. Gannoun-Zaki,, T. E. Wellems,, and K.W. Deitsch. 2003. Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron. J. Biol. Chem. 278:3412534132.
19. Chattopadhyay, R.,, A. Sharma,, V. K. Srivastava,, S. S. Pati,, S. K. Sharma,, B. S. Das,, and C. E. Chitnis. 2003. Plasmodium falciparum infection elicits both variant-specific and cross-reactive antibodies against variant surface antigens. Infect Immun. 71:597604.
20. Chen, Q.,, V. Fernandez,, A. Sundstrom,, M. Schlichtherle,, S. Datta,, P. Hagblom,, and M. Wahlgren. 1998. Developmental selection of var gene expression in Plasmodium falciparum. Nature 394:392395.
21. Clemson, C. M.,, J. A. McNeil,, H. F. Willard,, and J. B. Lawrence. 1996. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J. Cell Biol. 132:259275.
22. David, P. H.,, M. Hommel,, L. H. Miller,, I. J. Udeinya,, and L. D. Oligino. 1983. Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proc. Natl. Acad. Sci. USA 80: 50755079.
23. Deitsch, K. W.,, M. S. Calderwood,, and T. E. Wellems. 2001. Malaria. Cooperative silencing elements in var genes. Nature 412:875876.
24. Deitsch, K.W.,, A. del Pinal,, and T. E. Wellems. 1999. Intra-cluster recombination and var transcription switches in the antigenic variation of Plasmodium falciparum. Mol. Biochem. Parasitol. 101:107116.
25. Deitsch, K.W.,, E. R. Moxon,, and T. E. Wellems. 1997. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections. Microbiol. Mol. Biol. Rev. 61:281293.
26. Duffy, M. F.,, J. C. Reeder,, and G.V. Brown. 2003. Regulation of antigenic variation in Plasmodium falciparum: censoring freedom of expression? Trends Parasitol. 19:121124.
27. Feuerbach, F.,, V. Galy,, E. Trelles-Sticken,, M. Fromont-Racine,, A. Jacquier,, E. Gilson,, J. C. Olivo-Marin,, H. Scherthan,, and U. Nehrbass. 2002. Nuclear architecture and spatial positioning help establish transcriptional states of telomeres in yeast. Nat. Cell Biol. 4:214221.
28. Fidock, D.A.,, E. Bottius,, K. Brahimi,, I. I. Moelans,, M. Aikawa,, R. N. Konings,, U. Certa,, P. Olafsson,, T. Kaidoh,, and A. Asavanich. 1994. Cloning and characterization of a novel Plasmodium falciparum sporozoite surface antigen, STARP. Mol. Biochem. Parasitol. 64:219232.
29. Figueiredo, L. M.,, L. H. Freitas-Junior,, E. Bottius,, J. C. Olivo-Marin,, and A. Scherf. 2002. A central role for Plasmodium falciparum subtelomeric regions in spatial positioning and telomere length regulation. EMBO J. 21:815824.
30. Fischer, K.,, P. Horrocks,, M. Preuss,, J. Wiesner,, S. Wunsch,, A.A. Camargo,, and M. Lanzer. 1997. Expression of var genes located within polymorphic subtelomeric domains of Plasmodium falciparum chromosomes. Mol. Cell. Biol. 17:36793686.
31. Forsyth, K. P.,, G. Philip,, T. Smith,, E. Kum,, B. Southwell,, and G.V. Brown. 1989. Diversity of antigens expressed on the surface of erythrocytes infected with mature Plasmodium falciparum parasites in Papua New Guinea. Am. J. Trop. Med. Hyg. 41:259265.
32. Francis, N. J.,, and R. E. Kingston. 2001. Mechanisms of transcriptional memory. Nat. Rev. Mol. Cell Biol. 2:409421.
33. Freitas-Junior, L. H.,, E. Bottius,, L.A. Pirrit,, K.W. Deitsch,, C. Scheidig,, F. Guinet,, U. Nehrbass,, T. E. Wellems,, and A. Scherf. 2000. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407:10181022.
34. Fried, M.,, and P. E. Duffy. 1996. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272:15021504.
35. Gamain, B.,, J.D. Smith,, M. Avril,, D. I. Baruch,, A. Scherf,, J. Gysin,, and L. H. Miller. 2004. Identification of a 67-amino-acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates. Mol. Microbiol. 53:445455.
36. Gardner, J. P.,, R. A. Pinches,, D. J. Roberts,, and C. I. Newbold. 1996. Variant antigens and endothelial receptor adhesion in Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 93:35033508.
37. Gardner, M. J.,, N. Hall,, E. Fung,, O. White,, M. Berriman,, R.W. Hyman,, J. M. Carlton,, A. Pain,, K. E. Nelson,, S. Bowman,, I. T. Paulsen,, K. James,, J. A. Eisen,, K. Rutherford,, S. L. Salzberg,, A. Craig,, S. Kyes,, M. S. Chan,, V. Nene,, S. J. Shallom,, B. Suh,, J. Peterson,, S. Angiuoli,, M. Pertea,, J. Allen,, J. Selengut,, D. Haft,, M.W. Mather,, A. B. Vaidya,, D. M. Martin,, A. H. Fairlamb,, M. J. Fraunholz,, D. S. Roos,, S.A. Ralph,, G. I. McFadden,, L. M. Cummings,, G. M. Subramanian,, C. Mungall,, J. C. Venter,, D. J. Carucci,, S. L. Hoffman,, C. Newbold,, R.W. Davis,, C. M. Fraser,, and B. Barrell. 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498511.
38. Gatton, M. L.,, J. M. Peters,, E.V. Fowler,, and Q. Cheng. 2003. Switching rates of Plasmodium falciparum var genes: faster than we thought? Trends Parasitol. 19:202208.
39. Giha, H.A.,, T. Staalsoe,, D. Dodoo,, I.M. Elhassan,, C. Roper,, G. M. Satti,, D. E. Arnot,, T. G. Theander,, and L. Hviid. 1999. Nine-year longitudinal study of antibodies to variant antigens on the surface of Plasmodium falciparum-infected erythrocytes. Infect. Immun. 67:40924098.
40. Giha, H.A.,, T. G. Theander,, T. Staalso,, C. Roper,, I. M. Elhassan,, H. Babiker,, G. M. Satti,, D. E. Arnot,, and L. Hviid. 1998. Seasonal variation in agglutination of Plasmodium falciparum-infected erythrocytes. Am. J. Trop. Med. Hyg. 58:399405.
41. Grant, P. A. 2001. A tale of histone modifications. Genome Biol. 2:3.
42. Handunnetti, S. M.,, K. N. Mendis,, and P. H. David. 1987. Antigenic variation of cloned Plasmodium fragile in its natural host Macaca sinica. Sequential appearance of successive variant antigenic types. J. Exp. Med. 165:12691283.
43. Hediger, F.,, and S. M. Gasser. 2002. Nuclear organization and silencing: putting things in their place. Nat. Cell Biol. 4:5355.
44. Horrocks, P.,, R. Pinches,, S. Kyes,, N. Kriek,, S. Lee,, Z. Christodoulou,, and C. I. Newbold. 2002. Effect of var gene disruption on switching in Plasmodium falciparum. Mol. Microbiol. 45:11311141.
45. Horrocks, P.,, S. Kyes,, R. Pinches,, Z. Christodoulou,, and C. Newbold. 2004a. Transcription of a subtelomerically located var gene variant in Plasmodium falciparum appears to require the truncation of an adjacent var gene. Mol. Biochem. Parasitol. 134:193199.
46. Horrocks, P.,, R. Pinches,, Z. Christodoulou,, S.A. Kyes,, and C. I. Newbold. 2004b. Variable var transition rates underlie antigenic variation in malaria. Proc. Natl. Acad. Sci. USA 101:1112911134.
47. Jensen, A. T.,, P. Magistrado,, S. Sharp,, L. Joergensen,, T. Lavstsen,, A. Chiucchiuini,, A. Salanti,, L. S. Vestergaard,, J. P. Lusingu,, R. Hermsen,, R. Sauerwein,, J. Christensen,, M. A. Nielsen,, L. Hviid,, C. Sutherland,, T. Staalsoe,, and T. G. Theander. 2004. Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. J. Exp. Med. 199:11791190.
48. Jenuwein, T.,, and C.D. Allis. 2001.Translating the histone code. Science 293:10741080.
49. Kinyanjui, S. M.,, P. Bull,, C. I. Newbold,, and K. Marsh. 2003. Kinetics of antibody responses to Plasmodium falciparum-infected erythrocyte variant surface antigens. J. Infect. Dis. 187:667674.
50. Kirchmaier, A. L.,, and J. Rine. 2001. DNA replication- independent silencing in S. cerevisiae. Science 291:646650.
51. Kraemer, S. M.,, and J.D. Smith. 2003. Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family. Mol. Microbiol. 50:15271538.
52. Kriek, N.,, L. Tilley,, P. Horrocks,, R. Pinches,, B.C. Elford,, D. J. Ferguson,, K. Lingelbach,, and C. I. Newbold. 2003. Characterization of the pathway for transport of the cytoadherence-mediating protein, PfEMP1, to the host cell surface in malaria parasite-infected erythrocytes. Mol. Microbiol. 50: 12151227.
53. Kyes, S.,, P. Horrocks,, and C. Newbold. 2001. Antigenic variation at the infected red cell surface in malaria. Annu. Rev. Microbiol. 55:673707.
54. Kyes, S.,, R. Pinches,, and C. Newbold. 2000. A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum. Mol. Biochem. Parasitol. 105:311315.
55. Kyes, S. A.,, Z. Christodoulou,, A. Raza,, P. Horrocks,, R. Pinches,, J. A. Rowe,, and C. I. Newbold. 2003. A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern. Mol. Microbiol. 48:13391348.
56. Lavstsen, T.,, A. Salanti,, A.T. Jensen,, D. E. Arnot,, and T. G. Theander. 2003. Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions. Malar. J. 2:27.
57. Leech, J. H.,, J.W. Barnwell,, L. H. Miller,, and R. J. Howard. 1984. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J. Exp. Med. 159:15671575.
58. Li, Y. C.,, T. H. Cheng,, and M. R. Gartenberg. 2001. Establishment of transcriptional silencing in the absence of DNA replication. Science 291:650653.
59. Lindenthal, C.,, P. G. Kremsner,, and M. Q. Klinkert. 2003. Commonly recognised Plasmodium falciparum parasites cause cerebral malaria. Parasitol. Res. 91:363368.
60. Marsh, K.,, and R. J. Howard. 1986. Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants. Science 231:150153.
61. Mechali, M. 2001. DNA replication origins: from sequence specificity to epigenetics. Nat. Rev. Genet. 2:640645.
62. Miller, L. H.,, M. F. Good,, and G. Milon. 1994. Malaria pathogenesis. Science 2640:18781883.
63. Molineaux, L.,, H. H. Diebner,, M. Eichner,, W. E. Collins,, G. M. Jeffery,, and K. Dietz. 2001. Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology 122:379391.
64. Molineaux, L.,, and K. Dietz. 1999. Review of intra- host models of malaria. Parassitologia 41:221231.
65. Newbold, C.,, P. Warn,, G. Black,, A. Berendt,, A. Craig,, B. Snow,, M. Msobo,, N. Peshu,, and K. Marsh. 1997a. Receptor-specific adhesion and clinical disease in Plasmodium falciparum. Am. J. Trop. Med. Hyg. 57:389398.
66. Newbold, C. I.,, A.G. Craig,, S. Kyes,, A. R. Berendt,, R.W. Snow,, N. Peshu,, and K. Marsh. 1997b. PfEMP1,polymorphism and pathogenesis. Ann. Trop. Med. Parasitol. 91:551557.
67. Nielsen, M. A.,, T. Staalsoe,, J.A. Kurtzhals,, B. Q. Goka,, D. Dodoo,, M. Alifrangis,, T.G. Theander,, B. D. Akanmori,, and L. Hviid. 2002. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity. J. Immunol. 168:34443450.
68. Nielsen, M. A.,, L. S. Vestergaard,, J. Lusingu,, J. A. Kurtzhals,, H.A. Giha,, B. Grevstad,, B.Q. Goka,, M. M. Lemnge,, J. B. Jensen,, B. D. Akanmori,, T. G. Theander,, T. Staalsoe,, and L. Hviid. 2004. Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens. Infect. Immun. 72:35313535.
69. Nordstrand, A.,, A.G. Barbour,, and S. Bergstrom. 2000. Borrelia pathogenesis research in the postgenomic and post-vaccine era. Curr. Opin. Microbiol. 3:8692.
70. Noviyanti, R.,, G.V. Brown,, M. E. Wickham,, M. F. Duffy,, A. F. Cowman,, and J. C. Reeder. 2001. Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion. Mol. Biochem. Parasitol. 114:227237.
71. Oh, S. S.,, S. Voigt,, D. Fisher,, S. J. Yi,, P. J. LeRoy,, L. H. Derick,, S. Liu,, and A. H. Chishti. 2000. Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin-spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton. Mol. Biochem. Parasitol. 108:237247.
72. Paget-McNicol, S.,, M. Gatton,, I. Hastings,, and A. Saul. 2002. The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling. Parasitology 124:225235.
73. Peters, J.,, E. Fowler,, M. Gatton,, N. Chen,, A. Saul,, and Q. Cheng. 2002. High diversity and rapid changeover of expressed var genes during the acute phase of Plasmodium falciparum infections in human volunteers. Proc. Natl. Acad. Sci. USA 99:1068910694.
74. Recker, M.,, S. Nee,, P. C. Bull,, S. Kinyanjui,, K. Marsh,, C. Newbold,, and S. Gupta. 2004. Transient cross-reactive immune responses can orchestrate antigenic variation in malaria. Nature 429:555558.
75. Reeder, J. C.,, A. F. Cowman,, K. M. Davern,, J. G. Beeson,, J. K. Thompson,, S. J. Rogerson,, and G.V. Brown. 1999. The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1. Proc. Natl. Acad. Sci. USA 96:51985202.
76. Roberts, D. J.,, A. G. Craig,, A. R. Berendt,, R. Pinches,, G. Nash,, K. Marsh,, and C. I. Newbold. 1992. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357:689692.
77. Robinson, B. A.,, T. L. Welch,, and J. D. Smith. 2003. Widespread functional specialization of Plasmodium falciparum erythrocyte membrane protein 1 family members to bind CD36 analysed across a parasite genome. Mol. Microbiol. 47:12651278.
78. Rowe, A.,, J. Obeiro,, C. I. Newbold,, and K. Marsh. 1995. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect. Immun. 63: 23232326.
79. Rowe, J. A.,, and S. A. Kyes. 2004. The role of Plasmodium falciparum var genes in malaria in pregnancy. Mol. Microbiol. 53:10111019.
80. Rowe, J. A.,, S. A. Kyes,, S. J. Rogerson,, H. A. Babiker,, and A. Raza. 2002. Identification of a conserved Plasmodium falciparum var gene implicated in malaria in pregnancy. J. Infect. Dis. 185:12071211.
81. Rowe, J. A.,, J. M. Moulds,, C. I. Newbold,, and L. H. Miller. 1997. P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature 388:292295.
82. Salanti, A.,, A.T. Jensen,, H.D. Zornig,, T. Staalsoe,, L. Joergensen,, M.A. Nielsen,, A. Khattab,, D. E. Arnot,, M.Q. Klinkert,, L. Hviid,, and T.G. Theander. 2002. A sub-family of common and highly conserved Plasmodium falciparum var genes. Mol. Biochem. Parasitol. 122:111115.
83. Salanti, A.,, T. Staalsoe,, T. Lavstsen,, A.T. Jensen,, M. P. Sowa,, D. E. Arnot,, L. Hviid,, and T. G. Theander. 2003. Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol. Microbiol. 49:179191.
84. Scherf, A.,, L. M. Figueiredo,, and L. H. Freitas- Junior. 2001. Plasmodium telomeres: a pathogen’s perspective. Curr. Opin. Microbiol. 4:409414.
85. Scherf, A.,, R. Hernandez-Rivas,, P. Buffet,, E. Bottius,, C. Benatar,, B. Pouvelle,, J. Gysin,, and M. Lanzer. 1998. Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO J. 17:54185426.
86. Sleutels, F.,, R. Zwart,, and D. P. Barlow. 2002. The non-coding Air RNA is required for silencing autosomal imprinted genes Nature 415:810813.
87. Smith, J. D.,, C. E. Chitnis,, A. G. Craig,, D. J. Roberts,, D. E. Hudson-Taylor,, D. S. Peterson,, R. Pinches,, C. I. Newbold,, and L. H. Miller. 1995. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82:101110.
88. Smith, J. D.,, A. G. Craig,, N. Kriek,, D. Hudson- Taylor,, S. Kyes,, T. Fagen,, R. Pinches,, D. I. Baruch,, C. I. Newbold,, and L. H. Miller. 2000a. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc. Natl. Acad. Sci. USA 97:17661771.
89. Smith, J. D.,, S. Kyes,, A. G. Craig,, T. Fagan,, D. Hudson-Taylor,, L.H. Miller,, D. I. Baruch,, and C. I. Newbold. 1998. Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. Mol. Biochem. Parasitol. 97:133148.
90. Smith, J. D.,, G. Subramanian,, B. Gamain,, D. I. Baruch,, and L. H. Miller. 2000b. Classification of adhesive domains in the Plasmodium falciparum erythrocyte membrane protein 1 family. Mol. Biochem. Parasitol. 110:293310.
91. Springer, A. L.,, L. M. Smith,, D. Q. Mackay,, S. O. Nelson,, and J. D. Smith. 2004. Functional interdependence of the DBLβ domain and C2 region for binding of the Plasmodium falciparum variant antigen to ICAM-1. Mol. Biochem. Parasitol. 137:5564.
92. Su, X. Z.,, V. M. Heatwole,, S. P. Wertheimer,, F. Guinet,, J. A. Herrfeldt,, D. S. Peterson,, J. A. Ravetch,, and T. E. Wellems. 1995. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82:89100.
93. Taylor, H. M.,, S. A. Kyes,, and C. I. Newbold. 2000. Var gene diversity in Plasmodium falciparum is generated by frequent recombination events. Mol. Biochem. Parasitol. 110:391397.
94. Tebo, A. E.,, P. G. Kremsner,, K. P. Piper,, and A. J. Luty. 2002. Low antibody responses to variant surface antigens of Plasmodium falciparum are associated with severe malaria and increased susceptibility to malaria attacks in Gabonese children. Am. J. Trop. Med. Hyg. 67:597603.
95. Turner, C.M. 1997. The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei. FEMS Microbiol. Lett. 153:227231.
96. Turner, C.M. 1999. Antigenic variation in Trypanosoma brucei infections: an holistic view. J. Cell Sci. 112:31873192.
97. Turner, G.D.,, H. Morrison,, M. Jones,, T. M. Davis,, S. Looareesuwan,, I.D. Buley,, K.C. Gatter,, C. I. Newbold,, S. Pukritayakamee,, and B. Nagachinta. 1994. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am.J. Pathol. 145:10571069.
98. Urban, B. C.,, D. J. Ferguson,, A. Pain,, N. Willcox,, M. Plebanski,, J. M. Austyn,, and D. J. Roberts. 1999. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400:7377.
99. Voss, T. S.,, M. Kaestli,, D. Vogel,, S. Bopp,, and H. P. Beck. 2003. Identification of nuclear proteins that interact differentially with Plasmodium falciparum var gene promoters. Mol. Microbiol. 48:15931607.
100. Voss, T. S.,, J. K. Thompson,, J. Waterkeyn,, I. Felger,, N. Weiss,, A. F. Cowman,, and H. P. Beck. 2000. Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5′ flanking sequences. Mol. Biochem. Parasitol. 107:103115.
101. Waller, K. L.,, W. Nunomura,, B. M. Cooke,, N. Mohandas,, and R. L. Coppel. 2002. Mapping the domains of the cytoadherence ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) that bind to the knob-associated histidine-rich protein (KAHRP). Mol. Biochem. Parasitol.119:125129.

Tables

Generic image for table
TABLE 1

promoter-type and exon 1 comparison for polymorphic genes in 3D7 genome

Citation: Horrocks P, Kyes S, Bull P, Deitsch K. 2005. Molecular Aspects of Antigenic Variation in , p 399-415. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch21
Generic image for table
TABLE 2

promoter-type and exon 1 comparison for polymorphic genes in 3D7 genome, conserved within and between genomes

Citation: Horrocks P, Kyes S, Bull P, Deitsch K. 2005. Molecular Aspects of Antigenic Variation in , p 399-415. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch21

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