Antigenic Variation and the Genetics and Epigenetics of the PfEMP1 Erythrocyte Surface Antigens in Plasmodium falciparum Malaria

Advances in Applied Microbiology

Volumn 74, Issue , 2011, Pages 77-96

  Arnot, David E ^a,b,c   Jensen, Anja T R ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Rigshospitalet   (Denmark)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ERYTHROCYTE MEMBRANE PROTEIN 1; MEMBRANE ANTIGEN; PARASITE ANTIGEN; PROTOZOAL PROTEIN;

ANTIGEN EXPRESSION; ANTIGENIC VARIATION; BOOK; DISEASE TRANSMISSION; DNA BINDING MOTIF; EPIGENETICS; GENE; GENE EXPRESSION; GENETIC TRANSCRIPTION; GENOMICS; HUMAN; IMMUNE RESPONSE; MALARIA FALCIPARUM; MITOTIC RECOMBINATION; MULTIGENE FAMILY; NONHUMAN; PATHOGENESIS; PLASMODIUM KNOWLESI; PLASMODIUM VIVAX; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTOZOAL GENETICS; PULSED FIELD GEL ELECTROPHORESIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; VAR GENE; ANIMAL; ERYTHROCYTE; PLASMODIUM FALCIPARUM;

PLASMODIUM FALCIPARUM;

ANIMALS; ANTIGENIC VARIATION; ANTIGENS, PROTOZOAN; ANTIGENS, SURFACE; ERYTHROCYTES; HUMANS; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM; PROTOZOAN PROTEINS;

EID: 79953181986     PISSN: 00652164     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-387022-3.00007-0     Document Type: Chapter

References (108)

1. Aguas R., White L.J., Snow R.W., Gomes M.G. Prospects for malaria eradication in sub-Saharan Africa. PLoS ONE 2008, 3:e1767.
2. Aikawa M., Rabbege J.R., Udeinya I., Miller L.H. Electron microscopy of knobs in Plasmodium falciparum-infected erythrocytes. J. Parasitol. 1983, 69:435-437.
3. Aponte J.J., Menendez C., Schellenberg D., Kahigwa E., Mshinda H., Vountasou P., Tanner M., Alonso P.L. Age interactions in the development of naturally acquired immunity to Plasmodium falciparum and its clinical presentation. PLoS Med. 2007, 4:e242.
4. Arnot D.E., Gull K. The Plasmodium cell-cycle: Facts and questions. Ann. Trop. Med. Parasitol. 1998, 92:361-365.
5. Arnot D.E., Ronander E., Bengtsson D.C. The progression of the intra-erythrocytic cell cycle of Plasmodium falciparum and the role of the centriolar plaques in asynchronous mitotic division during schizogony. Int. J. Parasitol. 2011, 41:71-80.
6. Babiker H.A., Lines J., Hill W.G., Walliker D. Population structure of Plasmodium falciparum in villages with different malaria endemicity in east Africa. Am. J. Trop. Med. Hyg. 1997, 56:141-147.
7. Baird J.K. Age and 'strain-transcending' immunity to Plasmodium falciparum. Parasitol. Today 1994, 10:302.
8. Barbera M.A., Petes T.D. Selection and analysis of spontaneous reciprocal mitotic cross-overs in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 2006, 103:12819-12824.
9. Barnwell J.W., Howard R.J., Coon H.G., Miller L.H. Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria. Infect. Immun. 1983, 40:985-994.
10. Baum J., Papenfuss A.T., Mair G.R., Janse C.J., Vlachou D., Waters A.P., Cowman A.F., Crabb B.S., De Koning-Ward T.F. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 2009, 37:3788-3798.
11. Bengtsson D., Sowa K.M., Salanti A., Jensen A.T., Joergensen L., Turner L., Theander T.G., Arnot D.E. A method for visualizing surface-exposed and internal PfEMP1 adhesion antigens in Plasmodium falciparum infected erythrocytes. Malar. J. 2008, 7:101.
12. Bouharoun-Tayoun H., Attanath P., Sabchareon A., Chongsuphajaisiddhi T., Druilhe P. Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J. Exp. Med. 1990, 172:1633-1641.
13. Bozdech Z., Llinas M., Pulliam B.L., Wong E.D., Zhu J., Derisi J.L. The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 2003, 1:5.
14. Brolin K.J., Ribacke U., Nilsson S., Ankarklev J., Moll K., Wahlgren M., Chen Q. Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites. Genome Biol. 2009, 10:R117.
15. Brown K.N., Brown I.N. Immunity to malaria: Antigenic variation in chronic infections of Plasmodium knowlesi. Nature 1965, 208:1286-1288.
16. Brown K.N., Hills L.A. Antigenic variation and immunity to Plasmodium knowlesi: antibodies which induce antigenic variation and antibodies which destroy parasites. Trans. R. Soc. Trop. Med. Hyg. 1974, 68:139-142.
17. Brown K.N., Tanaka A. Vaccination against Plasmodium knowlesi malaria. Trans. R. Soc. Trop. Med. Hyg. 1975, 69:350-353.
18. Bull P.C., Lowe B.S., Kortok M., Molyneux C.S., Newbold C.I., Marsh K. Parasite antigens on the infected red cell are targets for naturally acquired immunity to malaria. Nat. Med. 1998, 4:358-360.
19. Bull P.C., Lowe B.S., Kortok M., Marsh K. Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in Kenya: Evidence for rare and prevalent variants. Infect. Immun. 1999, 67:733-739.
20. Bull P.C., Kortok M., Kai O., Ndungu F., Ross A., Lowe B.S., Newbold C.I., Marsh K. Plasmodium falciparum-infected erythrocytes: Agglutination by diverse Kenyan plasma is associated with severe disease and young host age. J. Infect. Dis. 2000, 182:252-259.
21. Bull P.C., Berriman M., Kyes S., Quail M.A., Hall N., Kortok M.M., Marsh K., Newbold C.I. Plasmodium falciparum variant surface antigen expression patterns during malaria. PLoS Pathog. 2005, 1:e26.
22. Calderwood M.S., Gannoun-Zaki L., Wellems T.E., Deitsch K.W. 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. 2003, 278:34125-34132.
23. Carlton J.M. Toward a malaria haplotype map. Nat. Genet. 2007, 39:5-6.
24. Carlton J.M., Escalante A.A., Neafsey D., Volkman S.K. Comparative evolutionary genomics of human malaria parasites. Trends Parasitol. 2008, 24:545-550.
25. Chen Q. The naturally acquired immunity in severe malaria and its implication for a PfEMP-1 based vaccine. Microbes Infect. 2007, 9:777-783.
26. Chen Q., Fernandez V., Sundström A., Schlichtherle M., Datta S., Hagblom P., Wahlgren M. Developmental selection of var gene expression in Plasmodium falciparum. Nature 1998, 394:392-395.
27. Chitnis C.E., Miller L.H. Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. J. Exp. Med. 1994, 180:497-506.
28. Chookajorn T., Dzikowski R., Frank M., Li F., Jiwani A.Z., Hartl D.L., Deitsch K.W. Epigenetic memory at malaria virulence genes. Proc. Natl. Acad. Sci. USA 2007, 104:899-902.
29. Cohen S., Butcher G.A. Serum antibody in acquired malarial immunity. Trans. R. Soc. Trop. Med. Hyg. 1971, 65:125-135.
30. Cohen S., McGregor I.A., Carrington S. Gammaglobulin and acquired immunity to human malaria. Nature 1961, 192:733-737.
31. Cohen J., Nussenzweig V., Nussenzweig R., Vekemans J., Leach A. From the circumsporozoite protein to the RTS, S/AS candidate vaccine. Hum. Vaccin. 2010, 6:90-96.
32. Cui L., Miao J. Chromatin-mediated epigenetic regulation in the malaria parasite Plasmodium falciparum. Eukaryot. Cell 2010, 9:1138-1149.
33. Dahlbäck M., Lavstsen T., Salanti A., Hviid L., Arnot D.E., Theander T., Nielsen M.A. Changes in var gene mRNA levels during erythrocytic development in two phenotypically distinct Plasmodium falciparum parasites. Malar. J. 2007, 6:78.
34. Deitsch K.W., Del Pinal A., Wellems T.E. Intra-cluster recombination and var transcription switches in the antigenic variation of Plasmodium falciparum. Mol. Biochem. Parasitol. 1999, 101:107-116.
35. Dietz K., Raddatz G., Molineaux L. Mathematical model of the first wave of Plasmodium falciparum asexual parasitemia in non-immune and vaccinated individuals. Am. J. Trop. Med. Hyg. 2006, 75:46-55.
36. Doolan D.L., Dobano C., Baird J.K. Acquired immunity to malaria. Clin. Microbiol. Rev. 2009, 22:13-36.
37. Duffy M.F., Byrne T.J., Carret C., Ivens A., Brown G.V. Ectopic recombination of a malaria var gene during mitosis associated with an altered var switch rate. J. Mol. Biol. 2009, 389:453-469.
38. Duffy M.F., Brown G.V., Basuki W., Krejany E.O., Noviyanti R., Cowman A.F., Reeder J.C. Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Mol. Microbiol. 2002, 43:1285-1293.
39. Duffy M.F., Byrne T.J., Elliott S.R., Wilson D.W., Rogerson S.J., Beeson J.G., Noviyanti R., Brown G.V. Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype. Mol. Microbiol. 2005, 56:774-788.
40. Duraisingh M.T., Voss T.S., Marty A.J., Duffy M.F., Good R.T., Thompson J.K., Freitas-Junior L.H., Scherf A., Crabb B.S., Cowman A.F. Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Cell 2005, 121:13-24.
41. Dzikowski R., Deitsch K.W. Active transcription is required for maintenance of epigenetic memory in the malaria parasite Plasmodium falciparum. J. Mol. Biol. 2008, 382:288-297.
42. Epp C., Li F., Howitt C.A., Chookajorn T., Deitsch K.W. Chromatin associated sense and antisense noncoding RNAs are transcribed from the var gene family of virulence genes of the malaria parasite Plasmodium falciparum. RNA 2009, 15:116-127.
43. Frank M., Dzikowski R., Constantini D., Amulic B., Berdougo E., Deitsch K. Strict pairing of var promoters and introns is required for var gene silencing in the malaria parasite Plasmodium falciparum. J. Biol. Chem. 2006, 281:9942-9952.
44. Freitas-Junior L.H., Bottius E., Pirrit L.A., Deitsch K.W., Scheidig C., Guinet F., Nehrbass U., Wellems T.E., Scherf A. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 2000, 407:1018-1022.
45. Freitas-Junior L.H., Hernandez-Rivas R., Ralph S.A., Montiel-Condado D., Ruvalcaba-Salazar O.K., Rojas-Meza A.P., Mancio-Silva L., Leal-Silvestre R.J., Gontijo A.M., Shorte S., Scherf A. Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell 2005, 121:25-36.
46. Gamain B., Trimnell A.R., Scheidig C., Scherf A., Miller L.H., Smith J.D. Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites. J. Infect. Dis. 2005, 191:1010-1013.
47. Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W., Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K., et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002, 419:498-511.
48. Higgins M.K. The structure of a chondroitin sulfate-binding domain important in placental malaria. J. Biol. Chem. 2008, 283:21842-21846.
49. Horrocks P., Kyes S., Pinches R., Christodoulou Z., Newbold C. Transcription of subtelomerically located var gene variant in Plasmodium falciparum appears to require the truncation of an adjacent var gene. Mol. Biochem. Parasitol. 2004, 134:193-199.
50. Horrocks P., Wong E., Russell K., Emes R.D. Control of gene expression in Plasmodium falciparum-Ten years on. Mol. Biochem. Parasitol. 2009, 164:9-25.
51. Hviid L. Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop. 2005, 95:270-275.
52. Hviid L., Staalsoe T. Malaria immunity in infants: A special case of a general phenomenon?. Trends Parasitol. 2004, 20:66-72.
53. Jeffery G.M. Epidemiological significance of repeated infections with homologous and heterologous strains and species of Plasmodium. Bull. World Health Organ. 1966, 35:873-882.
54. Jensen A.T.R., Magistrado P.A., Sharp S., Joergensen L., Lavstsen T., Chiucchiuini A., Salanti A., Vestergaard L.S., Lusingu J.P., Hermsen R., Sauerwein R., Christensen J., et al. Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by Group A var genes. J. Exp. Med. 2004, 199:1179-1190.
55. Joergensen L.M., Salanti A., Dobrilovic T., Barfod L., Hassenkam T., Theander T.G., Hviid L., Arnot D.E. The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs. Malar. J. 2010, 9:100.
56. Joergensen L., Bengtsson D.C., Bengtsson A., Ronander E., Berger S.S., Turner L., Dalgaard M.B., Cham G.K., Victor M.E., Lavstsen T., Theander T.G., Arnot D.E., et al. Surface co-expression of two different PfEMP1 antigens on single Plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. PLoS Pathogens. 2010, 6(9):e1001083.
57. Keightley P.D., Otto S.P. Interference among deleterious mutations favours sex and recombination in finite populations. Nature 2006, 443:89-92.
58. Kerr P.J., Ranford-Cartwright L.C., Walliker D. Proof of intragenic recombination in Plasmodium falciparum. Mol. Biochem. Parasitol. 1994, 66:241-248.
59. Khunrae P., Dahlback M., Nielsen M.A., Andersen G., Ditlev S.B., Resende M., Pinto V.V., Theander T.G., Higgins M.K., Salanti A. Full-length recombinant Plasmodium falciparum VAR2CSA binds specifically to CSPG and induces potent parasite adhesion-blocking antibodies. J. Mol. Biol. 2010, 397:826-834.
60. Kraemer S.M., Smith J.D. Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family. Mol. Microbiol. 2003, 50:1527-1538.
61. Kriek N., Tilley L., Horrocks P., Pinches R., Elford B.C., Ferguson D.J.P., Lingelbach K., Newbold C.I. Characterization of the pathway for transport of the cytoadherence-mediating protein, PfEMP1, to the host cell surface in malaria parasite-infected erythrocytes. Mol. Microbiol. 2003, 50:1215-1227.
62. Kyes S., Pinches R., Newbold C. A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum. Mol. Biochem. Parasitol. 2000, 105:311-315.
63. Kyes S., Horrocks P., Newbold C. Antigenic variation at the infected red cell surface in malaria. Annu. Rev. Microbiol. 2001, 55:673-707.
64. Kyes S.A., Christodoulou Z., Raza A., Horrocks P., Pinches R., Rowe J.A., Newbold C.I. A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern. Mol. Microbiol. 2003, 48:1339-1348.
65. Lavstsen T., Salanti A., Jensen A.T.R., Arnot D.E., Theander T.G. Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions. Malar. J. 2003, 2:27.
66. Lavstsen T., Magistrado P., Hermsen C.C., Salanti A., Jensen A.T.R., Sauerwein R., Hviid L., Theander T.G., Staalsoe T. Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans. Malar. J. 2005, 4:21.
67. Leech J.H., Barnwell J.W., Miller L.H., Howard R.J. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J. Exp. Med. 1984, 159:1567-1575.
68. Li F., Sonbuchner L., Kyes S.A., Epp C., Deitsch K.W. Nuclear non-coding RNAs are transcribed from the centromeres of Plasmodium falciparum and are associated with centromeric chromatin. J. Biol. Chem. 2008, 283:5692-5698.
69. Marsh K., Howard R.J. Antigens induced on erythrocytes by P. falciparum: Expression of diverse and conserved determinants. Science 1986, 231:150-153.
70. Marsh K., Kinyanjui S. Immune effector mechanisms in malaria. Parasite Immunol. 2006, 28:51-60.
71. Merrick C.J., Duraisingh M.T. Epigenetics in Plasmodium: What do we really know?. Eukaryot. Cell 2010, 9:1150-1158.
72. Merrick C.J., Dzikowski R., Imamura H., Chuang J., Deitsch K., Duraisingh M.T. The effect of Plasmodium falciparum Sir2a histone deacetylase on clonal and longitudinal variation in expression of the var family of virulence genes. Int. J. Parasitol. 2010, 40:35-43.
73. Miao J., Fan Q., Cui L., Li J., Li J., Cui L. The malaria parasite Plasmodium falciparum histones: Organization, expression, and acetylation. Gene 2006, 369:53-65.
74. Molineaux L., Diebner H.H., Eichner M., Collins W.E., Jeffery G.M., Dietz K. Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology 2001, 122:379-391.
75. Morrison L.J., Majiwa P., Read A.F., Barry J.D. Probabilistic order in antigenic variation of Trypanosoma brucei. Int. J. Parasitol. 2005, 35:961-972.
76. Mu J., Duan J., Makova K.D., Joy D.A., Huynh C.Q., Branch O.H., Li W.H., Su X.Z. Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum. Nature 2002, 418:323-324.
77. Mu J., Awadalla P., Duan J., McGee K.M., Joy D.A., McVean G.A., Su X.Z. Recombination hotspots and population structure in Plasmodium falciparum. PLoS Biol. 2005, 3:e335.
78. Nielsen M.A., Staalsoe T., Kurtzhals J.A.L., Goka B.Q., Dodoo D., Alifrangis M., Theander T.G., Akanmori B.D., Hviid L. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and non-severe malaria and is modified by acquired immunity. J. Immunol. 2002, 168:3444-3450.
79. Noviyanti R., Brown G.V., Wickham M.E., Duffy M.F., Cowman A.F., Reeder J.C. Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion. Mol. Biochem. Parasitol. 2001, 114:227-237.
80. Peters J., Fowler E., Gatton M., Chen N., Saul A., Cheng Q. 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 2002, 99:10689-10694.
81. Petes T.D., Pukkila P.J. Meiotic sister chromatid recombination. Adv. Genet. 1995, 33:41-62.
82. Prensier G., Slomianny C. The karyotype of Plasmodium falciparum determined by ultrastructural serial sectioning and 3D reconstruction. J. Parasitol. 1986, 72:731-736.
83. Ptashne M. On the use of the word 'epigenetic'. Curr. Biol. 2007, 17:R233-R236.
84. Ptashne M. Binding reactions: Epigenetic switches, signal transduction and cancer. Curr. Biol. 2009, 19:R234-R241.
85. Ralph S.A., Bischoff E., Mattei D., Sismeiro O., Dillies M.A., Guigon G., Coppee J.Y., David P.H., Scherf A. Transcriptome analysis of antigenic variation in Plasmodium falciparum-var silencing is not dependent on antisense RNA. Genome Biol. 2005, 6:R93.
86. Ralph S.A., Scheidig-Benatar C., Scherf A. Antigenic variation in Plasmodium falciparum is associated with movement of var loci between subnuclear locations. Proc. Natl. Acad. Sci. USA 2005, 102:5414-5419.
87. Salanti A., Jensen A.T.R., Zornig H.D., Staalsoe T., Joergensen L., Nielsen M.A., Khattab A., Arnot D.E., Klinkert M.Q., Hviid L., Theander T.G. A sub-family of common and highly conserved var genes expressed by CSA-adhering Plasmodium falciparum. Mol. Biochem. Parasitol. 2002, 122:111-115.
88. Salanti A., Staalsoe T., Lavstsen T., Jensen A.T.R., Sowa M.P.K., Arnot D.E., Hviid L., Theander T.G. Selective upregulation of a single distinctly structured var gene in CSA-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol. Microbiol. 2003, 49:179-191.
89. Sander A.F., Salanti A., Lavstsen T., Nielsen M.A., Magistrado P., Lusingu J., Ndam N.T., Arnot D.E. Multiple var2csa-type PfEMP1 genes located at different chromosomal loci occur in many Plasmodium falciparum isolates. PLoS ONE 2009, 4:e6667.
90. Scherf A., Mattei D. Cloning and characterization of chromosome breakpoints of Plasmodium falciparum: Breakage and new telomere formation occurs frequently and randomly in subtelomeric genes. Nucleic Acids Res. 1992, 20:1491-1496.
91. Scherf A., Hernandez-Rivas R., Buffet P., Bottius E., Benatar C., Pouvelle B., Gysin J., Lanzer M. Antigenic variation in malaria: In situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO J. 1998, 17:5418-5428.
92. Smith J.D., Chitnis C.E., Craig A.G., Roberts D.J., Hudson-Taylor D.E., Peterson D.S., Pinches R., Newbold C.I., Miller L.H. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 1995, 82:101-110.
93. Smith J.D., Gamain B., Baruch D.I., Kyes S. Decoding the language of var genes and Plasmodium falciparum sequestration. Trends Parasitol. 2001, 17:538-545.
94. Staalsoe T., Giha H.A., Dodoo D., Theander T.G., Hviid L. Detection of antibodies to variant antigens on Plasmodium falciparum infected erythrocytes by flow cytometry. Cytometry 1999, 35:329-336.
95. Staalsoe T., Hamad A.A., Hviid L., Elhassan I.M., Arnot D.E., Theander T.G. In vivo switching between variant surface antigens in human Plasmodium falciparum infection. J. Infect. Dis. 2002, 186:719-722.
96. Staalsoe T., Shulman C.E., Bulmer J.N., Kawuondo K., Marsh K., Hviid L. Variant surface antigen-specific IgG and protection against the clinical consequences of pregnancy-associated Plasmodium falciparum malaria. Lancet 2004, 363:283-289.
97. Su X., Heatwole V.M., Wertheimer S.P., Guinet F., Herrfeldt J.A., Peterson D.S., Ravetch J.A., Wellems T.E. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 1995, 82:89-100.
98. Su X., Ferdig M.T., Huang Y., Huynh C.Q., Liu A., You J., Wootton J.C., Wellems T.E. A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum. Science 1999, 286:1351-1353.
99. Tanabe K., Sakihama N., Rooth I., Bjorkman A., Farnert A. High frequency of recombination-driven allelic diversity and temporal variation of Plasmodium falciparum msp1 in Tanzania. Am. J. Trop. Med. Hyg. 2007, 76:1037-1045.
100. Taylor H.M., Kyes S.A., Harris D., Kriek N., Newbold C.I. A study of var gene transcription in vitro using universal var gene primers. Mol. Biochem. Parasitol. 2000, 105:13-23.
101. Templeton T.J. The varieties of gene amplification, diversification and hypervariability in the human malaria parasite, Plasmodium falciparum. Mol. Biochem. Parasitol. 2009, 166:109-116.
102. Tonkin C.J., Carret C.K., Duraisingh M.T., Voss T.S., Ralph S.A., Hommel M., Duffy M.F., Silva L.M., Scherf A., Ivens A., Speed T.P., Beeson J.G., et al. Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. PLoS Biol. 2009, 7:e84.
103. Triglia T., Wellems T.E., Kemp D.J. Towards a high-resolution map of the Plasmodium falciparum genome. Parasitol. Today 1992, 8:225-229.
104. Voss T.S., Healer J., Marty A.J., Duffy M.F., Thompson J.K., Beeson J.G., Reeder J.C., Crabb B.S., Cowman A.F. A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 2005, 439:1004-1008.
105. Vosshall L.B., Stocker R.F. Molecular architecture of smell and taste in Drosophila. Annu. Rev. Neurosci. 2007, 30:505-533.
106. Walliker D., Quakyi I.A., Wellems T.E., McCutchan T.F., Szarfman A., London W.T., Corcoran L.M., Burkot T.R., Carter R. Genetic analysis of the human malaria parasite Plasmodium falciparum. Science 1987, 236:1661-1666.
107. Wang C.W., Hermsen C.C., Sauerwein R.W., Arnot D.E., Theander T.G., Lavstsen T. The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer. Parasitol. Int. 2009, 58:478-480.
108. Wellems T.E., Panton L.J., Gluzman I.Y., Do R.V., Gwadz R.W., Walker-Jonah A., Krogstad D.J. Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Nature 1990, 345:253-255.