The practical implication of a clonal population structure is that biological characteristics can be attributed to a genetically well-defined subset of the parasitic population. In the case of Toxoplasma, the relationships between the three main lineages and some biological characteristics are now well established.
Virulence in mice is the most recognized phenotypic marker: type I strain led to a widespread parasite dissemination and death of mice less than 10 days after inoculation of < 10 tachyzoites; in contrast, mice survived to infection with a type II strain (50 percent lethal dose (LD50) > 103) and tachyzoite dissemination was much less extensive. Type III is also generally considered as avirulent in mice, although progressive deterioration and death of mice, notably with neurological symptoms, can occur a few weeks or months after inoculation. The genetic differences between strains elicit a different immune response in the host that could in part explain the different patterns of virulence (Gavrilescu and Denkers, 2001; Fux et al., 2003; Nguyen et al., 2003; Diana et al., 2004; Robben et al., 2004; Saeij et al., 2005a).
The higher virulence of type I in mice compared with types II or III has been correlated with in vitro biological properties: type I displays enhanced migration in vitro, as well as enhanced transmigration across polarized MDCK or across extracellular matrix. It also shows a higher rate of ex vivo penetration of lamina propria and submucosa (Barragan and Sibley, 2002). This ability to cross epithelial barriers rapidly and reach the bloodstream within hours post-infection might be an important predeterminant of parasite dissemination in vivo in susceptible host species. In cell culture, type I grows faster than type II or III and has a lower rate of interconversion from tachyzoite to bradyzoite than type II strains (Soete et al., 1993). The higher growth rate of type I parasites has been suggested to be due to a higher reinvasion rate rather than to a shorter doubling time (Saeij et al., 2005a).
Although these in vitro studies demonstrate different intrinsic properties of the different strains, the host response is essential for expression of virulence: strain virulence is not the same across host species - for example, type I strains, which are highly virulent in mice, are not pathogenic in rats (Zenner et al., 1999).
Atypical and naturally recombinant strains are usually more virulent in mice than are types II or III; however, owing to their genomic diversity they cannot be directly compared. They exhibit differences in mouse virulence and in other biological properties which probably reflect the differences in the combination of genes they have inherited (Grigg and Suzuki, 2003). Experimental crosses should prove useful in mapping the relationships between genotype and phenotype, and identifying 'virulence genes'. Interestingly, a cross between two avirulent strains, ME49 (type II) and CEP (type III), gave rise either to avirulent progeny like their parents or to progeny with enhanced virulence (Grigg et al., 2001a). Remarkable differences in the dissemination patterns in mice were observed between a virulent progenitor from a type II x III cross (LD50 was at least three logs lower than that of either parents) and its nonvirulent siblings strain (Saeij et al., 2005b).
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