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ANTIGENIC VARIATION AT THE STRUCTURAL AND FUNCTIONAL LEVEL 91<br />

is a venereal disease of horses in Africa. The predominantly<br />

tsetse-<strong>trans</strong>mitted trypanosomes<br />

can also be passed directly from mammal to<br />

mammal, by syringe, by carnivorous eating<br />

habits, and possibly <strong>trans</strong>placentally.<br />

Trypanosoma brucei is the most widely studied<br />

of the African trypanosomes, because it is<br />

by far the most convenient laboratory model.<br />

Although it is the least prevalent of the three<br />

major species of veterinary importance (the<br />

other two being T. congolense and T. vivax), it is<br />

the species that contains the two recognized<br />

subspecies that infect humans, T. brucei rhodesiense<br />

and T. brucei gambiense. The entire life<br />

cycle of T. brucei can be reproduced in the laboratory,<br />

using rodents and tsetse, but not yet<br />

entirely in cell culture. Both the bloodstream<br />

forms and the tsetse midgut ‘procyclic’ form<br />

can be readily cultivated in vitro, which allows<br />

genetic manipulations to be performed in a relatively<br />

facile manner. Relatively facile means<br />

they can be genetically manipulated with about<br />

10% the convenience of Saccharomyces cerevisiae,<br />

but more than ten times the ease with<br />

which similar manipulations can be performed<br />

in the human malaria parasite Plasmodium<br />

falciparum. Other apicomplexan parasites,<br />

especially Toxoplasma gondii, can be more<br />

readily manipulated than Plasmodium, and<br />

can be informative about the functions of<br />

some genes and organelles that are conserved<br />

between Plasmodium and Toxoplasma.<br />

ANTIGENIC VARIATION AT<br />

THE STRUCTURAL AND<br />

FUNCTIONAL LEVEL<br />

The variant surface glycoprotein coat<br />

Animal-infective bloodstream and tsetse<br />

salivary-gland ‘metacyclic’ trypanosomes are<br />

characterized by an electron-dense ‘surface<br />

coat’ (Figure 5.1). The surface coat of an individual<br />

trypanosome consists of about 10 million<br />

molecules of a single molecular species of variant<br />

surface glycoprotein (VSG). Antigenic variation<br />

involves the sequential expression of coats<br />

composed of different VSGs. Mice can be totally<br />

protected against homologous challenge by<br />

FIGURE 5.1 The surface structure of T. brucei bloodstream forms. A cross-section through the cell body and the<br />

flagellum shows the cell membrane with its underlying microtubular cytoskeleton and overlying surface coat at<br />

(A) low and (B) high magnifications. The approximate cross-sectional dimensions in (A) are 1 2 m.<br />

MOLECULAR BIOLOGY

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