Plasmodium falciparum merozoite surface protein 8 is a ring-stage membrane protein that localizes to the parasitophorous vacuole of infected erythrocytes.
To date, the following seven glycosylphosphatidylinositol (GPI)-anchored merozoite antigens have been described in Plasmodium falciparum: merozoite-associated surface protein 1 (MSP-1), MSP-2, MSP-4, MSP-5, MSP-8, MSP-10, and the rhoptry-associated membrane antigen. Of these, MSP-1, MSP-8, and MSP-10 possess a double epidermal growth factor (EGF)-like domain at the C terminus, and these modules are considered potential targets of protective immunity. In this study, we found that surprisingly, P. falciparum MSP-8 is transcribed and translated in the ring stage and is absent from the surface of merozoites. MSP-8 is the only GPI-anchored protein known to be expressed at this time. It is synthesized as a mature 80-kDa protein which is rapidly processed to a C-terminal 17-kDa species that contains the double EGF module. As determined by a combination of immunofluorescence and membrane purification approaches, it appears likely that MSP-8 initially localizes to the parasite plasma membrane in the ring stage. Although the C-terminal 17-kDa fragment is present in more mature stages, at these times it is found in the food vacuole. We successfully disrupted the MSP-8 gene in P. falciparum, a process that validated the specificity of the antibodies used in this study and also demonstrated that MSP-8 does not play a role essential to maintenance of the erythrocyte cycle. This finding, together with the observation that MSP-8 is exclusively intracellular, casts doubt over the viability of this antigen as a vaccine. However, it is still possible that MSP-8 is involved in an early parasitophorous vacuole function that is significant for pathogenesis in the human host.
The Walter & Eliza Hall Institute for Medical Research, 1G Royal Parade, Parkville, VIC 3050, Australia.
Damien R
DR
Drew
Paul R
PR
Sanders
Brendan S
BS
Crabb
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D020066:Merozoite Surface Protein 1 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry*; D014176:Protein Biosynthesis; D015800:Protozoan Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D011817:Rabbits; D014158:Transcription, Genetic; D014617:Vacuoles / Q000737:chemistry* / Q000469:parasitology
D000953:Antigens, Protozoan; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C431669:merozoite surface protein 8, Plasmodium