Antigenic variation in Plasmodium falciparum.

Biggs, Beverley‐Ann; Goozé, Lisa; Wycherley, Kaye; Wollish, Wendy S.; Southwell, Bridget R.; Leech, James H.; Brown, Graham V.

doi:10.1073/pnas.88.20.9171

Cited by 446 publications

(116 citation statements)

References 25 publications

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“…Resistance to all antimalarial drugs arises rapidly and is mediated by mutations in key target (Peterson et al, 1990;Wang et al, 1997) or transport genes (Foote et al, 1990;Fidock et al, 2000). Antigenic variation in key proteins is the basis of immune evasion (Biggs et al, 1991) and may in part explain the lack of sterilizing immunity in humans (Bruce-Chwatt, 1963;Neva, 1977;Marsh, 1992). Thus, mutation is a key virulence determinant in the parasite.…”

Section: Introductionmentioning

confidence: 99%

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Volkman

Lozovsky

Barry

et al. 2007

Gene

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The density and distribution of single-nucleotide polymorphisms (SNPs) across the genome has important implications for linkage disequilibrium mapping and association studies, and the level of simple-sequence microsatellite polymorphisms has important implications for the use of oligonucleotide hybridization methods to genotype SNPs. To assess the density of these types of polymorphisms in P. falciparum, we sampled introns and noncoding DNA upstream and downstream of coding regions among a variety of geographically diverse parasites. Across 36,229 base pairs of noncoding sequence representing 41 genetic loci, a total of 307 polymorphisms including 248 polymorphic microsatellites and 39 SNPs were identified. We found a significant excess of microsatellite polymorphisms having a repeat unit length of one or two, compared to those with longer repeat lengths, as well as a nonrandom distribution of SNP polymorphisms. Almost half of the SNPs localized to only three of the 41 genetic loci sampled. Furthermore, we find significant differences in the frequency of polymorphisms across the two chromosomes (2 and 3) examined most extensively, with an excess of SNPs and a surplus of polymorphic microsatellites on chromosome 3 as compared to chromosome 2 (P = 0.0001). Furthermore, at some individual genetic loci we also find a nonrandom distribution of polymorphisms between coding and flanking noncoding sequences, where completely monomorphic regions may flank highly polymorphic genes. These data, combined with our previous findings of nonrandom distribution of SNPs across chromosome 2, suggest that the Plasmodium falciparum genome may be a mosaic with regard to genetic diversity, containing chromosomal regions that are highly polymorphic interspersed with regions that are much less polymorphic.

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Section: Introductionmentioning

confidence: 99%

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Volkman

Lozovsky

Barry

et al. 2007

Gene

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“…All three properties have been implicated as virulence factors in human malaria Langreth & Peterson 1985;MacPherson et al 1985;Carlson et al 1990;Rowe et al 1995;Roberts et al 2000;Pain et al 2001). Finally, both species provoke strain-specific immunity (Taliaferro 1949;Jeffery 1966;Jarra & Brown 1985;Snounou et al 1989;Mota et al 1998), and both species undergo clonal antigenic variation (McLean et al 1982;Biggs et al 1991;Roberts et al 1992). However, there are some marked differences between P. falciparum in the field and P. chabaudi in laboratory mice.…”

Section: Plasmodium Chabaudi As a Model For Virulence Evolutionmentioning

confidence: 99%

“…Like cytoadherence, perhaps the most compelling evidence that antigenic variation confers a fitness advantage is its prevalence throughout the Plasmodium genus. Evidence for antigenic variation exists in all species of parasite studied (P. berghei (Cox 1962); P. knowlesi (Brown & Brown 1965); P. cynomolgi (Voller & Rossan 1969); P. falciparum Biggs et al 1991;Roberts et al 1992); P. chabaudi (McLean et al 1982); P. fragile (Handunetti et al 1987); and probably P. vivax del Portillo et al 2001)). Different sets of genes are responsible in different species (Howard & Barnwell 1985;al-Khedery et al 1999;del Portillo et al 2001;Janssen et al 2001Janssen et al , 2002, suggesting convergent evolution for this phenotype.…”

Section: (B) Antigenic Variationmentioning

confidence: 99%

Virulence in malaria: an evolutionary viewpoint

Mackinnon

Read

2004

Phil. Trans. R. Soc. Lond. B

227

205

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Malaria parasites cause much morbidity and mortality to their human hosts. From our evolutionary perspective, this is because virulence is positively associated with parasite transmission rate. Natural selection therefore drives virulence upwards, but only to the point where the cost to transmission caused by host death begins to outweigh the transmission benefits. In this review, we summarize data from the laboratory rodent malaria model, Plasmodium chabaudi, and field data on the human malaria parasite, P. falciparum, in relation to this virulence trade-off hypothesis. The data from both species show strong positive correlations between asexual multiplication, transmission rate, infection length, morbidity and mortality, and therefore support the underlying assumptions of the hypothesis. Moreover, the P. falciparum data show that expected total lifetime transmission of the parasite is maximized in young children in whom the fitness cost of host mortality balances the fitness benefits of higher transmission rates and slower clearance rates, thus exhibiting the hypothesized virulence trade-off. This evolutionary explanation of virulence appears to accord well with the clinical and molecular explanations of pathogenesis that involve cytoadherence, red cell invasion and immune evasion, although direct evidence of the fitness advantages of these mechanisms is scarce. One implication of this evolutionary view of virulence is that parasite populations are expected to evolve new levels of virulence in response to medical interventions such as vaccines and drugs.

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“…Since the host develops an antibody response against these parasite proteins over a period of time, the parasite constantly switches to different adherent phenotypes by expressing proteins with different receptor specificity through the use of its extensive and diverse var gene repertoire (3)(4)(5)(6)(7)(8)(9)(10)(11). Thus, in pregnant women, P. falciparum exploits the chondroitin 4-sulfate (C4S) 1 chains in an opportunistic manner to colonize in the placenta (12)(13)(14), which leads to poor fetal outcome and severe health problems in the mother (15)(16)(17).…”

mentioning

confidence: 99%

Structural Requirements for the Adherence ofPlasmodium falciparum-infected Erythrocytes to Chondroitin Sulfate Proteoglycans of Human Placenta

Alkhalil¹,

Achur²,

Valiyaveettil³

et al. 2000

Journal of Biological Chemistry

107

157

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Plasmodium falciparum infection during pregnancy results in the accumulation of infected red blood cells (IRBCs) in the placenta, leading to poor pregnancy outcome. In the preceding paper (Achur, R.N., Valiyaveettil, M., Alkhalil, A., Ockenhouse, C. F., and Gowda, D.C. (2000) J. Biol. Chem. 275, 40344 -40356), we reported that unusually low sulfated chondroitin sulfate proteoglycans (CSPGs) in the intervillous spaces of the placenta mediate the IRBC adherence. In this study, we report the structural requirements for the adherence and the minimum chondroitin 4-sulfate (C4S) structural motif that supports IRBC adherence. Partially sulfated C4Ss with varying sulfate contents were prepared by solvolytic desulfation of a fully sulfated C4S. These and other nonmodified C4Ss, with different proportions of 4-, 6-, and nonsulfated disaccharide repeats, were analyzed for inhibition of IRBC adherence to the placental CSPG. C4Ss containing 30 -50% 4-sulfated and 50 -70% nonsulfated disaccharide repeats efficiently inhibited IRBC adherence; C6S had no inhibitory activity. Oligosaccharides of varying sizes were prepared by the partial depolymerization of C4Ss containing varying levels of 4-sulfation, and their ability to inhibit the IRBC adherence was studied. Oligosaccharides with six or more disaccharide repeats inhibited IRBC adherence to the same level as that of the intact C4Ss, indicating that a dodecasaccharide is the minimum structural motif required for optimal IRBC adherence. Of the C4S dodecasaccharides, only those with two or three sulfate groups per molecule showed maximum IRBC inhibition. These data define the structural requirements for the IRBC adherence to placental CSPGs with implications for the development of therapeutics for maternal malaria.

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Antigenic variation in Plasmodium falciparum.

Cited by 446 publications

References 25 publications

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Virulence in malaria: an evolutionary viewpoint

Structural Requirements for the Adherence ofPlasmodium falciparum-infected Erythrocytes to Chondroitin Sulfate Proteoglycans of Human Placenta

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