Hypervariability within the Rifin, Stevor and Pfmc-2TM superfamilies in Plasmodium falciparum
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TLDR
Evidence is presented that the Stevor and Pfmc-2TM families are exported to the erythrocyte membrane, thus supporting the hypothesis that host immune pressure drives antigenic diversity within the loop, and an examination of multiple P.falciparum isolates demonstrates that the hypervariable loop within Stevor et al. possesses sequence diversity across isolate boundaries.Abstract:
The human malaria parasite, Plasmodium falciparum, possesses a broad repertoire of proteins that are proposed to be trafficked to the erythrocyte cytoplasm or surface, based upon the presence within these proteins of a Pexel/VTS erythrocyte-trafficking motif This catalog includes large families of predicted 2 transmembrane (2TM) proteins, including the Rifin, Stevor and Pfmc-2TM superfamilies, of which each possesses a region of extensive sequence diversity across paralogs and between isolates that is confined to a proposed surface-exposed loop on the infected erythrocyte Here we express epitope-tagged versions of the 2TM proteins in transgenic NF54 parasites and present evidence that the Stevor and Pfmc-2TM families are exported to the erythrocyte membrane, thus supporting the hypothesis that host immune pressure drives antigenic diversity within the loop An examination of multiple Pfalciparum isolates demonstrates that the hypervariable loop within Stevor and Pfmc-2TM proteins possesses sequence diversity across isolate boundaries The Pfmc-2TM genes are encoded within large amplified loci that share profound nucleotide identity, which in turn highlight the divergences observed within the hypervariable loop The majority of Pexel/VTS proteins are organized together within sub-telomeric genome neighborhoods, and a mechanism must therefore exist to differentially generate sequence diversity within select genes, as well as within highly defined regions within these genesread more
Citations
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Journal ArticleDOI
Antigenic Variation in Plasmodium falciparum
TL;DR: Key regulatory mechanisms thought to be critical for monoallelic expression of var genes are highlighted and controversies surrounding var genetic elements in antigenic variation are discussed.
Journal ArticleDOI
Expression switching in the stevor and Pfmc-2TM superfamilies in Plasmodium falciparum
TL;DR: Evidence is provided that the stevor and Pfmc‐2TM gene families play a role in P. falciparum antigenic variation, and chromosomal telomeric deletions are common in clonal lines and result in a spectrum of deletion genotypes.
Journal ArticleDOI
RIFINs are adhesins implicated in severe Plasmodium falciparum malaria
Suchi Goel,Mia Palmkvist,Kirsten Moll,Nicolas Joannin,Patricia Lara,Reetesh Raj Akhouri,Nasim Moradi,Karin Öjemalm,Mattias Westman,Davide Angeletti,Hanna Kjellin,Janne Lehtiö,Ola Blixt,Lars Ideström,Carl G. Gahmberg,Jill R. Storry,Annika K. Hult,Martin L. Olsson,Gunnar von Heijne,IngMarie Nilsson,Mats Wahlgren +20 more
TL;DR: It is suggested that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.
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Variant surface antigens of Plasmodium falciparum and their roles in severe malaria
TL;DR: These variant surface antigens are suggested to mediate the sequestration of infected erythrocytes in the microvasculature and block the blood flow when binding is excessive.
Journal ArticleDOI
A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes.
Iñigo Angulo-Barturen,María Belén Jiménez-Díaz,Teresa Mulet,Joaquín Rullas,Esperanza Herreros,Santiago Ferrer,Elena Jimenez,Alfonso Mendoza,Javier Regadera,Philip J. Rosenthal,Ian Bathurst,David L. Pompliano,Federico Gómez de las Heras,Domingo Gargallo-Viola +13 more
TL;DR: Using this model, a reproducible assay of antimalarial activity useful for drug discovery is implemented and validated and demonstrates that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods.
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Genome sequence of the human malaria parasite Plasmodium falciparum
Malcolm J. Gardner,Neil Hall,Eula Fung,Owen White,Matthew Berriman,Richard W. Hyman,Jane M. Carlton,Arnab Pain,Karen E. Nelson,Sharen Bowman,Ian T. Paulsen,Keith D. James,Jonathan A. Eisen,Kim Rutherford,Steven L. Salzberg,Alister Craig,Sue Kyes,Man Suen Chan,Vishvanath Nene,Shamira J. Shallom,Bernard B. Suh,Jeremy Peterson,Samuel V. Angiuoli,Mihaela Pertea,Jonathan E. Allen,Jeremy D. Selengut,Daniel H. Haft,Michael W. Mather,Akhil B. Vaidya,David M. A. Martin,Alan H. Fairlamb,Martin Fraunholz,David S. Roos,Stuart A. Ralph,Geoffrey I. McFadden,Leda M. Cummings,G. Mani Subramanian,Christopher J. Mungall,J. Craig Venter,Daniel J. Carucci,Stephen L. Hoffman,Chris I. Newbold,Ronald W. Davis,Claire M. Fraser,Bart Barrell +44 more
TL;DR: The genome sequence of P. falciparum clone 3D7 is reported, which is the most (A + T)-rich genome sequenced to date and is being exploited in the search for new drugs and vaccines to fight malaria.
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