Plasmodium falciparum merozoite surface protein 8 is a ring-stage membrane protein that localizes to the parasitophorous vacuole of infected erythrocytes

Drew, DR; Sanders, PR; Crabb, BS

Author(s): Drew, DR; Sanders, PR; Crabb, BS;
Details: Publication Year 2005-07,Volume 73,Issue #7,Page 3912-3922
Journal Title: INFECTION AND IMMUNITY
Publication Type: Journal Article
Abstract: 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.
Publisher: AMER SOC MICROBIOLOGY
Keywords: C-TERMINAL FRAGMENT; INVASION-INHIBITORY ANTIBODIES; FACTOR-LIKE DOMAINS; MALARIAL INFECTION; PROTECTIVE ROLE; ANTIGEN; PARASITES; RAFTS; CHOLESTEROL; INDIVIDUALS
Publisher's Version: https://doi.org/10.1128/IAI.73.7.3912-3922.2005
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2005-07-01 12:00:00