1932

Abstract

Malaria is a significant threat throughout the developing world. Among the most fascinating aspects of the protozoan parasites responsible for this disease are the methods they employ to avoid the immune system and perpetuate chronic infections. Key among these is antigenic variation: By systematically altering antigens that are displayed to the host's immune system, the parasite renders the adaptive immune response ineffective. For , the species responsible for the most severe form of human malaria, this process involves a complicated molecular mechanism that results in continuously changing patterns of variant-antigen-encoding gene expression. Although many features of this process remain obscure, significant progress has been made in recent years to decipher various molecular aspects of the regulatory cascade that causes chronic infection.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-090816-093841
2017-09-08
2024-06-19
Loading full text...

Full text loading...

/deliver/fulltext/micro/71/1/annurev-micro-090816-093841.html?itemId=/content/journals/10.1146/annurev-micro-090816-093841&mimeType=html&fmt=ahah

Literature Cited

  1. Amit-Avraham I, Pozner G, Eshar S, Fastman Y, Kolevzon N. 1.  et al. 2015. Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum. PNAS 112:E982–91 [Google Scholar]
  2. Amulic B, Salanti A, Lavstsen T, Nielsen MA, Deitsch KW. 2.  2009. An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria. PLOS Pathog 5:e1000256 [Google Scholar]
  3. Avraham I, Schreier J, Dzikowski R. 3.  2012. Insulator-like pairing elements regulate silencing and mutually exclusive expression in the malaria parasite Plasmodium falciparum. PNAS 109:E3678–86 [Google Scholar]
  4. Bachmann A, Esser C, Petter M, Predehl S, von Kalckreuth V. 4.  et al. 2009. Absence of erythrocyte sequestration and lack of multicopy gene family expression in Plasmodium falciparum from a splenectomized malaria patient. PLOS ONE 4:e7459 [Google Scholar]
  5. Bachmann A, Predehl S, May J, Harder S, Burchard GD. 5.  et al. 2011. Highly co-ordinated var gene expression and switching in clinical Plasmodium falciparum isolates from non-immune malaria patients. Cell Microbiol. 13:1397–409 [Google Scholar]
  6. Bancells C, Deitsch KW. 6.  2013. A molecular switch in the efficiency of translation reinitiation controls expression of var2csa, a gene implicated in pregnancy-associated malaria. Mol. Microbiol. 90:472–88 [Google Scholar]
  7. Bartfai R, Hoeijmakers WA, Salcedo-Amaya AM, Smits AH, Janssen-Megens E. 7.  et al. 2010. H2A.Z demarcates intergenic regions of the Plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3. PLOS Pathog 6:e1001223 [Google Scholar]
  8. Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC. 8.  et al. 1995. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82:77–87 [Google Scholar]
  9. Baum J, Papenfuss AT, Mair GR, Janse CJ, Vlachou D. 9.  et al. 2009. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res 37:3788–98 [Google Scholar]
  10. Brancucci NM, Bertschi NL, Zhu L, Niederwieser I, Chin WH. 10.  et al. 2014. Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell Host Microbe 16:165–76 [Google Scholar]
  11. Brancucci NM, Witmer K, Schmid CD, Flueck C, Voss TS. 11.  2012. Identification of a cis-acting DNA-protein interaction implicated in singular var gene choice in Plasmodium falciparum. Cell Microbiol. 14:1836–48 [Google Scholar]
  12. Broadbent KM, Park D, Wolf AR, Van Tyne D, Sims JS. 12.  et al. 2011. A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs. Genome Biol 12:R56 [Google Scholar]
  13. Buratowski S. 13.  2009. Progression through the RNA polymerase II CTD cycle. Mol. Cell 36:541–46 [Google Scholar]
  14. Calderwood MS, Gannoun-Zaki L, Wellems TE, Deitsch KW. 14.  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. 278:34125–32 [Google Scholar]
  15. Campbell TL, De Silva EK, Olszewski KL, Elemento O, Llinas M. 15.  2010. Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite. PLOS Pathog 6:e1001165 [Google Scholar]
  16. Chakrabarti K, Pearson M, Grate L, Sterne-Weiler T, Deans J. 16.  et al. 2007. Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis. RNA 13:1923–39 [Google Scholar]
  17. Cho EJ. 17.  2007. RNA polymerase II carboxy-terminal domain with multiple connections. Exp. Mol. Med. 39:247–54 [Google Scholar]
  18. Chookajorn T, Dzikowski R, Frank M, Li F, Jiwani AZ. 18.  et al. 2007. Epigenetic memory at malaria virulence genes. PNAS 104:899–902 [Google Scholar]
  19. Coleman BI, Skillman KM, Jiang RH, Childs LM, Altenhofen LM. 19.  et al. 2014. A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. Cell Host Microbe 16:177–86 [Google Scholar]
  20. Cousins S. 20.  2016. Targets to reduce malaria unlikely to be met, says WHO. BMJ 355:i6668 [Google Scholar]
  21. Cowman AF, Healer J, Marapana D, Marsh K. 21.  2016. Malaria: biology and disease. Cell 167:610–24 [Google Scholar]
  22. Cunningham D, Fonager J, Jarra W, Carret C, Preiser P, Langhorne J. 22.  2009. Rapid changes in transcription profiles of the Plasmodium yoelii yir multigene family in clonal populations: lack of epigenetic memory?. PLOS ONE 4:e4285 [Google Scholar]
  23. Deitsch KW, Calderwood MS, Wellems TE. 23.  2001. Malaria: cooperative silencing elements in var genes. Nature 412:875–76 [Google Scholar]
  24. Deitsch KW, del Pinal A, Wellems TE. 24.  1999. Intra-cluster recombination and var transcription switches in the antigenic variation of Plasmodium falciparum. Mol. Biochem. Parasitol. 101:107–16 [Google Scholar]
  25. Deitsch KW, Lukehart SA, Stringer JR. 25.  2009. Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat. Rev. Microbiol. 7:493–503 [Google Scholar]
  26. Duffy MF, Brown GV, Basuki W, Krejany EO, Noviyanti R. 26.  et al. 2002. Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Mol. Microbiol. 43:1285–93 [Google Scholar]
  27. Duraisingh MT, Horn D. 27.  2016. Epigenetic regulation of virulence gene expression in parasitic protozoa. Cell Host Microbe 19:629–40 [Google Scholar]
  28. Duraisingh MT, Voss TS, Marty AJ, Duffy MF, Good RT. 28.  et al. 2005. Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Cell 121:13–24 [Google Scholar]
  29. Dzikowski R, Deitsch KW. 29.  2008. Active transcription is required for maintenance of epigenetic memory in the malaria parasite Plasmodium falciparum. J. Mol. Biol. 382:288–97 [Google Scholar]
  30. Dzikowski R, Frank M, Deitsch K. 30.  2006. Mutually exclusive expression of virulence genes by malaria parasites is regulated independently of antigen production. PLOS Pathog 2:e22 [Google Scholar]
  31. Dzikowski R, Li F, Amulic B, Eisberg A, Frank M. 31.  et al. 2007. Mechanisms underlying mutually exclusive expression of virulence genes by malaria parasites. EMBO Rep 8:959–65 [Google Scholar]
  32. Egloff S, Murphy S. 32.  2008. Cracking the RNA polymerase II CTD code. Trends Genet 24:280–88 [Google Scholar]
  33. Egloff S, O'Reilly D, Chapman RD, Taylor A, Tanzhaus K. 33.  et al. 2007. Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science 318:1777–79 [Google Scholar]
  34. Eick D, Geyer M. 34.  2013. The RNA polymerase II carboxy-terminal domain (CTD) code. Chem. Rev. 113:8456–90 [Google Scholar]
  35. Epp C, Li F, Howitt CA, Chookajorn T, Deitsch KW. 35.  2009. Chromatin associated sense and antisense noncoding RNAs are transcribed from the var gene family of virulence genes of the malaria parasite Plasmodium falciparum. RNA 15:116–27 [Google Scholar]
  36. Flueck C, Bartfai R, Volz J, Niederwieser I, Salcedo-Amaya AM. 36.  et al. 2009. Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors. PLOS Pathog 5:e1000569 [Google Scholar]
  37. Frank M, Dzikowski R, Amulic B, Deitsch K. 37.  2007. Variable switching rates of malaria virulence genes are associated with chromosomal position. Mol. Microbiol. 64:1486–98 [Google Scholar]
  38. Frank M, Dzikowski R, Constantini D, Amulic B, Burdougo E, Deitsch K. 38.  2006. Strict pairing of var promoters and introns is required for var gene silencing in the malaria parasite Plasmodium falciparum. J. Biol. Chem. 281:9942–52 [Google Scholar]
  39. Freitas-Junior LH, Bottius E, Pirrit LA, Deitsch KW, Scheidig C. 39.  et al. 2000. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407:1018–22 [Google Scholar]
  40. Gardner MJ, Hall N, Fung E, White O, Berriman M. 40.  et al. 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511 [Google Scholar]
  41. Ghorbal M, Gorman M, MacPherson CR, Martins RM, Scherf A, Lopez-Rubio JJ. 41.  2014. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat. Biotechnol. 32:819–21 [Google Scholar]
  42. Guizetti J, Barcons-Simon A, Scherf A. 42.  2016. trans-Acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite. Nucleic Acids Res. 44:9710–18 [Google Scholar]
  43. Gupta AP, Chin WH, Zhu L, Mok S, Luah YH. 43.  et al. 2013. Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum. PLOS Pathog. 9:e1003170 [Google Scholar]
  44. Hoeijmakers WA, Stunnenberg HG, Bartfai R. 44.  2012. Placing the Plasmodium falciparum epigenome on the map. Trends Parasitol 28:486–95 [Google Scholar]
  45. Horrocks P, Pinches R, Christodoulou Z, Kyes S, Newbold C. 45.  2004. Variable var transition rates underlie antigenic variation in malaria. PNAS 101:11129–34 [Google Scholar]
  46. Jensen AT, Magistrado P, Sharp S, Joergensen L, Lavstsen T. 46.  et al. 2004. Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. J. Exp. Med. 199:1179–90 [Google Scholar]
  47. Jiang L, Mu J, Zhang Q, Ni T, Srinivasan P. 47.  et al. 2013. PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum. Nature 499:223–27 [Google Scholar]
  48. Joergensen L, Bengtsson DC, Bengtsson A, Ronander E, Berger SS. 48.  et al. 2010. Surface co-expression of two different PfEMP1 antigens on single Plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. PLOS Pathog 6:e1001083 [Google Scholar]
  49. Kraemer SM, Smith JD. 49.  2003. Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family. Mol. Microbiol. 50:1527–38 [Google Scholar]
  50. Kyes S, Christodoulou Z, Pinches R, Kriek N, Horrocks P, Newbold C. 50.  2007. Plasmodium falciparum var gene expression is developmentally controlled at the level of RNA polymerase II-mediated transcription initiation. Mol. Microbiol. 63:1237–47 [Google Scholar]
  51. Kyes SA, Christodoulou Z, Raza A, Horrocks P, Pinches R. 51.  et al. 2003. A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern. Mol. Microbiol. 48:1339–48 [Google Scholar]
  52. Kyes SA, Kraemer SM, Smith JD. 52.  2007. Antigenic variation in Plasmodium falciparum: gene organization and regulation of the var multigene family. Eukaryot. Cell 6:1511–20 [Google Scholar]
  53. Lavstsen T, Salanti A, Jensen ATR, Arnot DE, Theander TG. 53.  2003. Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions. Malaria J. 2:27 [Google Scholar]
  54. Lomvardas S, Barnea G, Pisapia DJ, Mendelsohn M, Kirkland J, Axel R. 54.  2006. Interchromosomal interactions and olfactory receptor choice. Cell 126:403–13 [Google Scholar]
  55. Lopez-Rubio JJ, Gontijo AM, Nunes MC, Issar N, Hernandez RR, Scherf A. 55.  2007. 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites. Mol. Microbiol. 66:1296–305 [Google Scholar]
  56. Lopez-Rubio JJ, Mancio-Silva L, Scherf A. 56.  2009. Genome-wide analysis of heterochromatin associates clonally variant gene regulation with perinuclear repressive centers in malaria parasites. Cell Host. Microbe 5:179–90 [Google Scholar]
  57. Mbogning J, Page V, Burston J, Schwenger E, Fisher RP. 57.  et al. 2015. Functional interaction of Rpb1 and Spt5 C-terminal domains in co-transcriptional histone modification. Nucleic Acids Res 43:9766–75 [Google Scholar]
  58. Merrick CJ, Jiang RH, Skillman KM, Samarakoon U, Moore RM. 58.  et al. 2015. Functional analysis of sirtuin genes in multiple Plasmodium falciparum strains. PLOS ONE 10:e0118865 [Google Scholar]
  59. Miao J, Fan Q, Cui L, Li X, Wang H. 59.  et al. 2010. The MYST family histone acetyltransferase regulates gene expression and cell cycle in malaria parasite Plasmodium falciparum. Mol. Microbiol. 78:883–902 [Google Scholar]
  60. Miller LH, Baruch DI, Marsh K, Doumbo OK. 60.  2002. The pathogenic basis of malaria. Nature 415:673–79 [Google Scholar]
  61. Miller LH, Good MF, Milon G. 61.  1994. Malaria pathogenesis. Science 264:1878–83 [Google Scholar]
  62. Mok BW, Ribacke U, Rasti N, Kironde F, Chen Q. 62.  et al. 2008. Default pathway of var2csa switching and translational repression in Plasmodium falciparum. PLOS ONE 3:e1982 [Google Scholar]
  63. Montgomery J, Mphande FA, Berriman M, Pain A, Rogerson SJ. 63.  et al. 2007. Differential var gene expression in the organs of patients dying of falciparum malaria. Mol. Microbiol. 65:959–67 [Google Scholar]
  64. Mourier T, Carret C, Kyes S, Christodoulou Z, Gardner PP. 64.  et al. 2008. Genome-wide discovery and verification of novel structured RNAs in Plasmodium falciparum. Genome Res 18:281–92 [Google Scholar]
  65. Navarro M, Gull K. 65.  2001. A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature 414:759–63 [Google Scholar]
  66. Ng HH, Robert F, Young RA, Struhl K. 66.  2003. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11:709–19 [Google Scholar]
  67. Noble R, Christodoulou Z, Kyes S, Pinches R, Newbold CI, Recker M. 67.  2013. The antigenic switching network of Plasmodium falciparum and its implications for the immuno-epidemiology of malaria. eLife 2:e01074 [Google Scholar]
  68. Otto TD, Wilinski D, Assefa S, Keane TM, Sarry LR. 68.  et al. 2010. New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-seq. Mol. Microbiol. 76:12–24 [Google Scholar]
  69. Perez-Toledo K, Rojas-Meza AP, Mancio-Silva L, Hernandez-Cuevas NA, Delgadillo DM. 69.  et al. 2009. Plasmodium falciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9 and is linked to mutually exclusive expression of var genes. Nucleic Acids Res. 37:2596–606 [Google Scholar]
  70. Petter M, Lee CC, Byrne TJ, Boysen KE, Volz J. 70.  et al. 2011. Expression of P. falciparum var genes involves exchange of the histone variant H2A.Z at the promoter. PLOS Pathog 7:e1001292 [Google Scholar]
  71. Petter M, Selvarajah SA, Lee CC, Chin WH, Gupta AP. 71.  et al. 2013. H2A.Z and H2B.Z double-variant nucleosomes define intergenic regions and dynamically occupy var gene promoters in the malaria parasite Plasmodium falciparum. Mol. Microbiol. 87:1167–82 [Google Scholar]
  72. Ponts N, Fu L, Harris EY, Zhang J, Chung DW. 72.  et al. 2013. Genome-wide mapping of DNA methylation in the human malaria parasite Plasmodium falciparum. Cell Host Microbe 14:696–706 [Google Scholar]
  73. Prucca CG, Slavin I, Quiroga R, Elias EV, Rivero FD. 73.  et al. 2008. Antigenic variation in Giardia lamblia is regulated by RNA interference. Nature 456:750–54 [Google Scholar]
  74. Rai R, Zhu L, Chen H, Gupta AP, Sze SK. 74.  et al. 2014. Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle. BMC Genom 15:959 [Google Scholar]
  75. Ralph SA, Scheidig-Benatar C, Scherf A. 75.  2005. Antigenic variation in Plasmodium falciparum is associated with movement of var loci between subnuclear locations. PNAS 102:5414–19 [Google Scholar]
  76. Recker M, Buckee CO, Serazin A, Kyes S, Pinches R. 76.  et al. 2011. Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern. PLOS Pathog 7:e1001306 [Google Scholar]
  77. Rottmann M, Lavstsen T, Mugasa JP, Kaestli M, Jensen AT. 77.  et al. 2006. Differential expression of var gene groups is associated with morbidity caused by Plasmodium falciparum infection in Tanzanian children. Infect. Immun. 74:3904–11 [Google Scholar]
  78. Salanti A, Dahlback M, Turner L, Nielsen MA, Barfod L. 78.  et al. 2004. Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J. Exp. Med. 200:1197–203 [Google Scholar]
  79. Salanti A, Staalsoe T, Lavstsen T, Jensen ATR, Sowa MPK. 79.  et al. 2003. Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol. Microbiol. 49:179–91 [Google Scholar]
  80. Salcedo-Amaya AM, van Driel MA, Alako BT, Trelle MB, van den Elzen AM. 80.  et al. 2009. Dynamic histone H3 epigenome marking during the intraerythrocytic cycle of Plasmodium falciparum. PNAS 106:9655–60 [Google Scholar]
  81. Saraiya AA, Li W, Wang CC. 81.  2011. A microRNA derived from an apparent canonical biogenesis pathway regulates variant surface protein gene expression in Giardia lamblia. RNA 17:2152–64 [Google Scholar]
  82. Saraiya AA, Li W, Wu J, Chang CH, Wang CC. 82.  2014. The microRNAs in an ancient protist repress the variant-specific surface protein expression by targeting the entire coding sequence. PLOS Pathog 10:e1003791 [Google Scholar]
  83. Scherf A, Hernandez-Rivas R, Buffet P, Bottius E, Benatar C. 83.  et al. 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. 17:5418–26 [Google Scholar]
  84. Siegel TN, Hon CC, Zhang Q, Lopez-Rubio JJ, Scheidig-Benatar C. 84.  et al. 2014. Strand-specific RNA-Seq reveals widespread and developmentally regulated transcription of natural antisense transcripts in Plasmodium falciparum. BMC Genom 15:150 [Google Scholar]
  85. Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE. 85.  et al. 1995. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82:101–10 [Google Scholar]
  86. Smith JD, Craig AG, Kriek N, Hudson-Taylor D, Kyes S. 86.  et al. 2000. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. PNAS 97:1766–71 [Google Scholar]
  87. Su X, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JV. 87.  et al. 1995. A large and diverse gene family (var) encodes 200–350 kD proteins implicated in the antigenic variation and cytoadherence of Plasmodium falciparum-infected erythrocytes. Cell 82:89–100 [Google Scholar]
  88. Swamy L, Amulic B, Deitsch KW. 88.  2011. Plasmodium falciparum var gene silencing is determined by cis DNA elements that form stable and heritable interactions. Eukaryot. Cell 10:530–39 [Google Scholar]
  89. Tembo DL, Nyoni B, Murikoli RV, Mukaka M, Milner DA. 89.  et al. 2014. Differential PfEMP1 expression is associated with cerebral malaria pathology. PLOS Pathog 10:e1004537 [Google Scholar]
  90. Tonkin CJ, Carret CK, Duraisingh MT, Voss TS, Ralph SA. 90.  et al. 2009. Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. PLOS Biol. 7:e84 [Google Scholar]
  91. Ukaegbu UE, Kishore SP, Kwiatkowski DL, Pandarinath C, Dahan-Pasternak N. 91.  et al. 2014. Recruitment of PfSET2 by RNA polymerase II to variant antigen encoding loci contributes to antigenic variation in P. falciparum. PLOS Pathog. 10:e1003854 [Google Scholar]
  92. Ukaegbu UE, Zhang X, Heinberg AR, Wele M, Chen Q, Deitsch KW. 92.  2015. A unique virulence gene occupies a principal position in immune evasion by the malaria parasite Plasmodium falciparum. PLOS Genet. 11:e1005234 [Google Scholar]
  93. Upadhyay R, Bawankar P, Malhotra D, Patankar S. 93.  2005. A screen for conserved sequences with biased base composition identifies noncoding RNAs in the A–T rich genome of Plasmodium falciparum. Mol. Biochem. Parasitol. 144:149–58 [Google Scholar]
  94. Volz JC, Bartfai R, Petter M, Langer C, Josling GA. 94.  et al. 2012. PfSET10, a Plasmodium falciparum methyltransferase, maintains the active var gene in a poised state during parasite division. Cell Host Microbe 11:7–18 [Google Scholar]
  95. Voss TS, Healer J, Marty AJ, Duffy MF, Thompson JK. 95.  et al. 2006. A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 439:1004–8 [Google Scholar]
  96. Wagner JC, Platt RJ, Goldfless SJ, Zhang F, Niles JC. 96.  2014. Efficient CRISPR-Cas9-mediated genome editing in Plasmodium falciparum. Nat. Methods 11:915–18 [Google Scholar]
  97. Wang CW, Lavstsen T, Bengtsson DC, Magistrado PA, Berger SS. 97.  et al. 2012. Evidence for in vitro and in vivo expression of the conserved VAR3 (type 3) Plasmodiumfalciparum erythrocyte membrane protein 1. Malar. J. 11:129 [Google Scholar]
  98. Wassmer SC, Taylor TE, Rathod PK, Mishra SK, Mohanty S. 98.  et al. 2015. Investigating the pathogenesis of severe malaria: a multidisciplinary and cross-geographical approach. Am. J. Trop. Med. Hyg 9342–56 [Google Scholar]
  99. Wei G, Zhao Y, Zhang Q, Pan W. 99.  2015. Dual regulatory effects of non-coding GC-rich elements on the expression of virulence genes in malaria parasites. Infect. Genet. Evol. 36:490–99 [Google Scholar]
  100. Westenberger SJ, Cui L, Dharia N, Winzeler E, Cui L. 100.  2009. Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes. BMC Genom 10:610 [Google Scholar]
  101. Winter G, Chen QJ, Flick K, Kremsner P, Fernandez V, Wahlgren M. 101.  2003. The 3D7var5.2 (varCOMMON) type var gene family is commonly expressed in non-placental Plasmodium falciparum malaria. Mol. Biochem. Parasitol. 127:179–91 [Google Scholar]
  102. Zhang Q, Huang Y, Zhang Y, Fang X, Claes A. 102.  et al. 2011. A critical role of perinuclear filamentous actin in spatial repositioning and mutually exclusive expression of virulence genes in malaria parasites. Cell Host Microbe 10:451–63 [Google Scholar]
  103. Zhang Q, Siegel TN, Martins RM, Wang F, Cao J. 103.  et al. 2014. Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria. Nature 513:431–35 [Google Scholar]
  104. Zhang Y, Jiang N, Chang Z, Wang H, Lu H. 104.  et al. 2014. The var3 genes of Plasmodium falciparum 3D7 strain are differentially expressed in infected erythrocytes. Parasite 21:19 [Google Scholar]
/content/journals/10.1146/annurev-micro-090816-093841
Loading
/content/journals/10.1146/annurev-micro-090816-093841
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error