Spleen-Dependent Regulation of Antigenic Variation in Malaria Parasites: <i>Plasmodium knowlesi SICAvar</i> Expression Profiles in Splenic and Asplenic Hosts A. LappStacey Korir-MorrisonCindy JiangJianlin BaiYaohui CorredorVladimir GalinskiMary R. 2013 <div><p>Background</p><p>Antigenic variation by malaria parasites was first described in <i>Plasmodium knowlesi</i>, which infects humans and macaque monkeys, and subsequently in <i>P. falciparum</i>, the most virulent human parasite. The schizont-infected cell agglutination (SICA) variant proteins encoded by the <i>SICAvar</i> multigene family in <i>P. knowlesi</i>, and Erythrocyte Membrane Protein-1 (EMP-1) antigens encoded by the <i>var</i> multigene family in <i>P. falciparum</i>, are expressed at the surface of infected erythrocytes, are associated with virulence, and serve as determinants of naturally acquired immunity. A parental <i>P. knowlesi</i> clone, Pk1(A+), and a related progeny clone, Pk1(B+)1+, derived by an <i>in</i><i>vivo</i> induced variant antigen switch, were defined by the expression of distinct SICA variant protein doublets of 210/190 and 205/200 kDa, respectively. Passage of SICA[+] infected erythrocytes through splenectomized rhesus monkeys results in the SICA[-] phenotype, defined by the lack of surface expression and agglutination with variant specific antisera.</p> <p>Principal Findings</p><p>We have investigated <i>SICAvar</i> RNA and protein expression in Pk1(A+), Pk1(B+)1+, and SICA[-] parasites. The Pk1(A+) and Pk1(B+)1+ parasites express different distinct <i>SICAvar</i> transcript and protein repertoires. By comparison, SICA[-] parasites are characterized by a vast reduction in <i>SICAvar</i> RNA expression, the lack of full-length <i>SICAvar</i> transcript signals on northern blots, and correspondingly, the absence of any SICA protein detected by mass spectrometry.</p> <p>Significance</p><p>SICA protein expression may be under transcriptional as well as post-transcriptional control, and we show for the first time that the spleen, an organ central to blood-stage immunity in malaria, exerts an influence on these processes. Furthermore, proteomics has enabled the first in-depth characterization of SICA[+] protein phenotypes and we show that the <i>in</i><i>vivo</i> switch from Pk1(A+) to Pk1(B+)1+ parasites resulted in a complete change in SICA profiles. These results emphasize the importance of studying antigenic variation in the context of the host environment.</p> </div>