This research will be done primarily in Israel at Tel Aviv University in collaboration with Drs. Zvi Fishelson and Daniel Gold as an extension of NIH grant # R01AI46762. The blood fluke Schistosoma mansoni causes intestinal schistosomiasis, a parasitic disease affecting the lives of millions throughout Africa and South America. Young and adult worms of S. mansoni express on their surface several types of immune evasion molecules which protect them for at least 10 years within infected patients. SCIP-1 (Schistosome Complement Inhibitory Protein type 1) is a 94kDa protein functionally related to the human complement inhibitor CD59. A role for SCIP-1 has been postulated in the ability of the schistosome parasite to resist the effects of the complement membrane attack complex. The major aims of this proposed research are: a. to elucidate the interaction of SCIP-1 with components of the complement system, and b. to demonstrate the effect of SCIP-1 in cell culture and animal models. Data suggests that SCIP-1 is paramyosin (Pmy), an invertebrate muscular protein, and that it specifically binds to the C9 component of complement. The sites in SCIP-1/Pmy and C9 involved in their binding will be identified and the surface location of SCIP-1/Pmy on the larvae and worms will be analysed. Native and recombinant SCIP-1/Pmy will be transplanted into surrogate CD59-negative cells to study its effect on complement. Additionally, the protective efficacy of SCIP-1/Pmy will be evaluated in a mouse model of infection by passive and active immunization. This proposed research will contribute to our understanding of the immune evasion mechanisms of S. mansoni and to development of an immunotherapeutical approach against schistosomiasis.
| Deng, Jiusheng; Gold, Daniel; LoVerde, Philip T et al. (2007) Mapping of the complement C9 binding domain in paramyosin of the blood fluke Schistosoma mansoni. Int J Parasitol 37:67-75 |
| Deng, Jiusheng; Gold, Daniel; LoVerde, Philip T et al. (2003) Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin. Infect Immun 71:6402-10 |
