Trypanosome surface antigen (VSG) switching

Sleeping sickness in humans (and a related disease in cow) is caused by a unicellular parasite called trypanosome, which alternates between two hosts, tsetse fly and a mammal (Fig. 37.19). Trypanosome undergoes important biochemical changes involving diversity in the variable surface glycoprotein (VSG), a major component of surface coat, which provides antigenic reaction. Although, at any one time a trypanosome expresses only one VSG, its ability to change into any of the ~100 possible different VSGs is the secret of parasite's survival during fly-mammal cycle.

A tsetse fly, during a bite, gains the parasite, which loses its VSG but re-acquires a new VSG after three weeks when, it differentiates in 'metacyclic form'. This form enters mammalian bloodstream during a bite, where VSG keeps on changing every 1-2 weeks, so that the immune response always lags behind the change in VSG and the parasite evades the immune surveillance, perpetuating indefinitely, till it enters the central nervous system and often causes death.

Genes (about 1000) for ~ 100 different VSGs are present scattered on different chromosomes in the genome of trypanosome. Diversity, therefore, depends on changing expression from one pre-existing gene to another. Each VSG is coded by a single basic copy gene, which may be telomeric or internal in location, and there may be several isogenes for same VSG or similar VSGs. The copy of the gene, which is active, is called expression linked copy (ELC) and is located on an expression site. Creation of an ELC may involve transfer of a basic copy gene to the expression site or vice versa. Almost all switches in VSG type involve replacement of the ELC by a pre-existing silent copy.