Differentiation‐associated surface antigen variation in the ancient eukaryote <i>Giardia lamblia</i>

Svärd, Staffan G.; Meng, Tze‐Chiang; Hetsko, Michael L.; McCaffery, J. Michael; Gillin, Frances D.

doi:10.1046/j.1365-2958.1998.01125.x

Cited by 76 publications

(59 citation statements)

References 49 publications

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“…Density-dependent differentiation to a nondividing stage, although not evident in bacteria, is well documented in eukaryotic parasites. An interesting case is Giardia, which encysts with density dependence and appears to produce new antigenic variants upon excystation (53). Nevertheless, trypanosome antigenic variation differs from that of other pathogens in its likely scale, the repertoire consisting of up to 2,000 VSG genes, the majority of which are pseudogenes.…”

Section: Discussionmentioning

confidence: 99%

Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Lythgoe

Morrison

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et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Pathogens often persist during infection because of antigenic variation in which they evade immunity by switching between distinct surface antigen variants. A central question is how ordered appearance of variants, an important determinant of chronicity, is achieved. Theories suggest that it results directly from a complex pattern of transition connectivity between variants or indirectly from effects such as immune cross-reactivity or differential variant growth rates. Using a mathematical model based only on known infection variables, we show that order in trypanosome infections can be explained more parsimoniously by a simpler combination of two key parasite-intrinsic factors: differential activation rates of parasite variant surface glycoprotein (VSG) genes and densitydependent parasite differentiation. The model outcomes concur with empirical evidence that several variants are expressed simultaneously and that parasitaemia peaks correlate with VSG genes within distinct activation probability groups. Our findings provide a possible explanation for the enormity of the recently sequenced VSG silent archive and have important implications for field transmission.mathematical model ͉ Typanosoma brucei ͉ variant surface glycoprotein ͉ switching ͉ hierarchy

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Section: Discussionmentioning

confidence: 99%

Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Lythgoe

Morrison

Read

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…This investigation demonstrated that major surface antigen VSP C6 predominates in cysts but is downregulated during the process of excystation. Conversely, in vitro-maintained G. lamblia clone GS/ M-83-H7 (expressing VSP H7) did not change its surface antigen properties during life cycle stage transition (21).…”

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confidence: 93%

“…Surface antigen alterations were observed within proliferating populations of intestinal trophozoites (2,4,6,7,19), as well as among individual trophozoites upon the release from nonproliferative cysts (9,21). The latter phenomenon was investigated by monitoring vsp gene expression during in vitro en-and excystation of G. lamblia isolate WB, clone C6 (21). This investigation demonstrated that major surface antigen VSP C6 predominates in cysts but is downregulated during the process of excystation.…”

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confidence: 97%

“…VSP has a potential function in antigenic variation to circumvent the host immune response, and it may exhibit physiological functions important for the intestinal survival of the parasite within the host (14). Surface antigen alterations were observed within proliferating populations of intestinal trophozoites (2,4,6,7,19), as well as among individual trophozoites upon the release from nonproliferative cysts (9,21). The latter phenomenon was investigated by monitoring vsp gene expression during in vitro en-and excystation of G. lamblia isolate WB, clone C6 (21).…”

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confidence: 99%

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Experimental Infections of Neonatal Mice with Cysts of Giardia lamblia Clone GS/M-83-H7 Are Associated with an Antigenic Reset of the Parasite

et al. 2004

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Transmission of the protozoan parasite Giardia lamblia from one to another host individuum occurs through peroral ingestion of cysts which, following excystation in the small intestine, release two trophozoites each. Many studies have focused on the major surface antigen, VSP (for variant surface protein), which is responsible for the antigenic variability of the parasite. By using trophozoites of G. lamblia clone GS/M-83-H7 (expressing VSP H7) and the neonatal mouse model for experimental infections, we quantitatively assessed the process of antigenic variation of the parasite on the transcriptional level. In the present study, variant-specific regions identified on different GS/M-83-H7 vsp sequences served as targets for quantitative reverse transcription-PCR to monitor alterations in vsp mRNA levels during infection. Respective results demonstrated that antigenic switching of both the duodenal trophozoite and the cecal cyst populations was associated with a massive reduction in vsp H7 mRNA levels but not with a simultaneous increase in transcripts of any of the subvariant vsp genes analyzed. Most importantly, we also explored giardial variant-type formation and vsp mRNA levels after infection of mice with cysts. This infection mode led to an antigenic reset of the parasite in that a VSP H7-negative inoculum "converted" into a population of intestinal trophozoites that essentially consisted of the original VSP H7 type. This antigenic reset appears to be associated with excystation rather than with a selective process which favors expansion of a residual population of VSP H7 types within the antigenically diversified cyst inoculum. Based on these findings, the VSP H7 type has to be regarded as a predominant variant of G. lamblia clone GS/M-83-H7 which (re-)emerges during early-stage infection and may contribute to an optimal establishment of the parasite within the intestine of the experimental murine host.

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“…Indeed, such mechanisms have been repeatedly observed. For example, among protistan parasites, Trypanosomes typically express only one of thousands of variant surface glycoprotein genes (26); Giardia express only one of 30-150 variant-specific surface protein genes (27); ciliates also express only one of many genes encoding surface antigens (28).…”

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confidence: 99%

Host–parasite interactions and the evolution of ploidy

Nuismer

Otto²

2004

Proc. Natl. Acad. Sci. U.S.A.

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Although the majority of animals and plants, including humans, are dominated by the diploid phase of their life cycle, extensive diversity in ploidy level exists among eukaryotes, with some groups being primarily haploid whereas others alternate between haploid and diploid phases. Previous theory has illuminated conditions that favor the evolution of increased or decreased ploidy but has shed little light on which species should be primarily haploid and which primarily diploid. Here, we report a discovery that emerged from host-parasite models in which ploidy levels were allowed to evolve: selection is more likely to favor diploidy in host species and haploidy in parasite species. Essentially, when parasites must evade a host's immune system or defense response, selection favors parasitic individuals that express a narrow array of antigens and elicitors, thus favoring haploid parasites over diploid parasites. Conversely, when hosts must recognize a parasite before mounting a defensive response, selection favors hosts with a broader arsenal of recognition molecules, thus favoring diploid hosts over haploid hosts. These results are consistent with the predominance of haploidy among parasitic protists.

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Differentiation‐associated surface antigen variation in the ancient eukaryote Giardia lamblia

Cited by 76 publications

References 49 publications

Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation

Experimental Infections of Neonatal Mice with Cysts of Giardia lamblia Clone GS/M-83-H7 Are Associated with an Antigenic Reset of the Parasite

Host–parasite interactions and the evolution of ploidy

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