Blythe, J.E.; (2007) The stevor multigene family of Plasmodium falciparum . Doctoral thesis , University of London.

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Abstract

The stevor family is the third largest multigene family in the P. falciparum 3D7 genome (Gardner et al., 2002). With 30 copies estimated per genome, each encoding a predicted transmembrane spanning protein: a conserved N-terminal domain is followed by hydrophobic regions, a 100 amino acid 'hyper-variable' region (HVR), conserved transmembrane domain and short highly conserved cytoplasmic C-terminus. In 3D7, stevor is transcribed in trophozoites and STEVOR protein was found in cytoplasmic membranous structures known as Maurer's clefts (Kaviratne et al., 2002). The Maurer's clefts are implicated in trafficking of proteins to the infected red blood cell (iRBC) surface, and pre-assembly of proteins destined for knob structures on the surface (Craig and Scherf, 2001). Stevors have also been detected in gametocyte stages and a STEVOR peptide found in sporozoite extracts (Sutherland, 2002 and Florens et al, 2002). The HVR of STEVOR may play a role in immune evasion. To investigate this further, we have started to characterise the genomic repertoire and expression profile of stevor genes in laboratory lines and field parasite isolates from Kenya, East Africa. Using stevor specific primers, we have identified 152 stevors in P. falciparum laboratory lines and Kenyan isolates. In addition, 27 stevors were identified in the genome of a Ghanaian field isolate (www.plasmodb.org) and 17 in a second laboratory isolate IT. Western blots identified a protein of approximately 30 kDa expected STEVOR mean molecular mass is 36.75kDa. Immunofluorescence assays showed that in mature, segmented schizonts, STEVOR is redistributed from the Maurer's clefts to throughout the iRBC cytosol. Interestingly, STEVOR was also observed in the apex of merozoites. An extremely important observation for the application of in vitro cultured P. falciparum clones is the huge difference in STEVOR expression to that in the field parasite isolates. STEVOR protein is expressed in only 5% of P. falciparum 3D7 schizonts, whereas it is found in 50% of Kilifi field isolate schizonts. We investigated field isolates further to see whether STEVOR is on the iRBC surface together with other multigene families, such as the var encoded PfEMPl and RIFINS, where STEVOR could play a role in antigenic variation which enables the P. falciparum parasite to evade the host immune response. Alternatively, STEVOR may have ligand binding functions/ RBC adherence properties during final schizont stage, rupture and merozoite reinvasion.

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