While no phenotypic differences were observed between the gene-deletion mutants and wild-type (wt) parasites during development in the mosquito or in the liver, blood stages of the mutants exhibited an attenuated phenotype in mice. While wt-infected C57B/6 mice died 79 days post infection as a result of complications typical for experimental cerebral malaria, Pbsbp1-infected mice did not develop experimental cerebral malaria but died from hyperparasitemia 3245 days post infection, respectively. A similar attenuation was also observed in infections in Balb/c mice. The parasitemia in the Pbsbp1-infected mice was comparable to that of wt during the initial 2 days of infection, but was reduced compared with wt thereafter. Mutant parasites were predominantly found in reticulocytes throughout the course of infection, whereas virulent wt parasites were found in erythrocytes in the later course of infection.In addition, mice infected with the Pbsbp1 mutants showed a 3.6-fold increase in schizonts in the peripheral blood circulation compared to wt infections, respectively, indicating reduced sequestration of RBCs infected with mutant schizonts.Pbsbp1 parasites showed strongly reduced accumulation in the adipose tissue and lungs compared with wt, which is typical for a loss of CD36-mediated sequestration. Conversely, significantly increased accumulation of parasites was detected in the spleens of mice infected with Pbsbp1 mutants. Higher accumulation in the spleen of non-sequestered schizonts has been attributed to increased removal of non-sequestering schizonts by the spleen.Binding to mouse CD36 was significantly lower in Pbsbp1 schizonts compared with wt schizonts with both plate-coated CD36 or CD36 expressed on CHO-745 cells.

While no phenotypic differences were observed between the gene-deletion mutants and wild-type (wt) parasites during development in the mosquito or in the liver, blood stages of the mutants exhibited an attenuated phenotype in mice. While wt-infected C57B/6 mice died 79 days post infection as a result of complications typical for experimental cerebral malaria, Pbsbp1-infected mice did not develop experimental cerebral malaria but died from hyperparasitemia 3245 days post infection, respectively. A similar attenuation was also observed in infections in Balb/c mice. The parasitemia in the Pbsbp1-infected mice was comparable to that of wt during the initial 2 days of infection, but was reduced compared with wt thereafter. Mutant parasites were predominantly found in reticulocytes throughout the course of infection, whereas virulent wt parasites were found in erythrocytes in the later course of infection.In addition, mice infected with the Pbsbp1 mutants showed a 3.6-fold increase in schizonts in the peripheral blood circulation compared to wt infections, respectively, indicating reduced sequestration of RBCs infected with mutant schizonts.Pbsbp1 parasites showed strongly reduced accumulation in the adipose tissue and lungs compared with wt, which is typical for a loss of CD36-mediated sequestration. Conversely, significantly increased accumulation of parasites was detected in the spleens of mice infected with Pbsbp1 mutants. Higher accumulation in the spleen of non-sequestered schizonts has been attributed to increased removal of non-sequestering schizonts by the spleen.Binding to mouse CD36 was significantly lower in Pbsbp1 schizonts compared with wt schizonts with both plate-coated CD36 or CD36 expressed on CHO-745 cells.

Evidence is presented for:- reduced sequestration of blood stages in mice- enhanced survival of C57BL/6 mice (reduced MA-ARDS; lung pathology) - SBP-1-mediated sequestration is not essential for the development of pulmonary pathology but affects its resolution