Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria.
Variant antigens appear on the surface of Plasmodium knowlesi-infected erythrocytes as the asexual parasite matures and are detected by antibody-mediated schizont-infected cell agglutination (SICA). We now show that cloned parasites can undergo antigenic variation in nonsplenectomized monkeys. In addition, we previously described a new P. knowlesi phenotype in which uncloned parasites passaged in splenectomized monkeys were no longer agglutinable by immune sera. We have designated this new phenotype SICA[-] and the one expressing the variant antigen SICA[+]. Cloned parasites can also switch from SICA[+] to SICA[-] in splenectomized monkeys. The switch from SICA[+] to SICA[-] is a gradual process that requires sequential subpassage in several monkeys. After passage in one monkey, the agglutination titer decreased 4- to 16-fold. Decreased agglutination was associated with decreased antibody binding on all infected erythrocytes as measured by fluorescein-conjugated anti-rhesus monkey immunoglobulin. The asexual malaria parasite can therefore alter its expression of variant antigen in response to the host environment (antivariant antibody or splenectomy). When cloned SICA[-] parasites were inoculated into intact monkeys, two courses of parasitemia were observed: fulminant parasitemia (greater than 20%) and parasitemia that was controlled. Fulminant infections were associated with conversion of the parasite from SICA[-] to SICA[+], i.e., from nonexpression to expression of the variant antigen on the erythrocyte surface. Parasitized erythrocytes remained SICA[-] in those infections that were controlled. It appears, therefore, that the expression of the variant antigen on the erythrocyte surface may influence parasite virulence.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000939:Epitopes; D004910:Erythrocyte Membrane / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D014644:Genetic Variation; D006384:Hemagglutination; D008253:Macaca mulatta; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008297:Male; D010641:Phenotype; D010961:Plasmodium / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology*; D013156:Splenectomy; D014774:Virulence
D000941:Antigens; D000939:Epitopes