Protective immune responses against protease-like antigens of the murine malaria parasite Plasmodium vinckei

Gor, Dennis O.; Li, Albert C.; Rosenthal, Philip J.

doi:10.1016/s0264-410x(98)80119-9

Cited by 11 publications

(9 citation statements)

References 40 publications

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“…These SERA genes are arranged in a head-to-tail array with SERA and SERPH the fifth and sixth genes in the cluster, respectively. A similar cluster of five SERA-like genes has been identified in Plasmodium vivax (25), and further homologues have been discovered in the rodent malaria parasite Plasmodium vinckei (26). The presence of relatively large SERA multigene families in divergent Plasmodium species suggests an important biological role for the proteins encoded by these genes.…”

mentioning

confidence: 63%

“…Somewhat surprisingly, it is now apparent that the genome contains at least nine SERAlike genes, eight in a cluster on chromosome 2 and one on chromosome 9 (24) (PlasmoDB data base). Other Plasmodium species also appear to contain relatively large SERA gene families (25,26). Our interest in the work described here was to begin to explore the biological purpose of the P. falciparum SERA genes by analyzing expression profiles and potential functional redundancy across this family.…”

Section: Discussionmentioning

confidence: 99%

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A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

Miller¹,

Good

Drew³

et al. 2002

Journal of Biological Chemistry

160

173

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The Plasmodium falciparum serine repeat antigen (SERA) has shown considerable promise as a blood stage vaccine for the control of malaria. A related protein, SERPH, has also been described in P. falciparum. Whereas their biological role remains unknown, both proteins possess papain-like protease domains that may provide attractive targets for therapeutic intervention. Genomic sequencing has recently shown that SERA and SERPH are the fifth and sixth genes, respectively, in a cluster of eight SERA homologues present on chromosome 2. In this paper, the expression and functional relevance of these eight genes and of a ninth SERA homologue found on chromosome 9 were examined in blood stage parasites. Using reverse transcriptase-PCR and microarray approaches, we demonstrate that whereas mRNA to all nine SERA genes is synthesized late in the erythrocytic cycle, it is those genes in the central region of the chromosome 2 cluster that are substantially up-regulated at this time. Using antibodies specific to each SERA, it was apparent that SERA4 to -6, and possibly also SERA9, are synthesized in blood stage parasites. The reactivity of antibodies from malaria-immune individuals with the SERA recombinant proteins suggested that SERA2 and SERA3 are also expressed at least in some parasite populations. To examine whether SERA genes are essential to blood stage growth, each of the eight chromosome 2 SERA genes was targeted for disruption. Whereas genes at the periphery of the cluster were mostly dispensable (SERA2 and -3 and SERA7 and -8), those in the central region (SERA4 to -6) could not be disrupted. The inability to disrupt SERA4, -5, and -6 is consistent with their apparent dominant expression and implies an important role for these genes in maintenance of the erythrocytic cycle.

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mentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

Miller¹,

Good

Drew³

et al. 2002

Journal of Biological Chemistry

160

173

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“…For more than 10 years after the first description of a gene family member, the existence of the Plasmodium serine repeat antigen (SERA) multigene family has been overlooked. Serine repeat antigen family proteins share homology with the papain family of cysteine proteases (Kiefer et al, 1996;Gor et al, 1998;Bourgon et al, 2004;Arisue et al, 2007Arisue et al, , 2011. Almost all SERA genes are clustered in a head-to-tail manner and the number of SERA genes in the clustered region varies among parasite species (Bourgon et al, 2004;McCoubrie et al, 2007;Arisue et al, 2007Arisue et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

Arisue¹,

Palacpac²,

Tanabe³

et al. 2011

Gene Duplication

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“…The DNA encoding this second gene was used to screen an erythrocytic-stage P. 6i6ax (Salvador I strain) uZAP cDNA library (kindly provided by M. Kieffer) and isolate a gene encoding a SERA homologue (SERPH vivax ; GenBank accession number AF052747). We also identified genes encoding three SERA homologues from a P. 6inckei genomic DNA library [15] (SERA vinckei 1 -3; GenBank accession numbers U59860, U59861 and U59862). Our comparison of the protease domains of described SERA homologues (the sequence of the SERA-3 protease domain is not available) identified two subclasses of proteins, represented by P. falciparum SERA and SERPH ( Table 1).…”

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confidence: 99%

“…To allow a comparison of known features of SERA and SERPH with those of a P. 6inckei homologue, we generated antisera against the E. coliexpressed protease domain of SERA vinckei -1. The protein was expressed in BL21(DE3)pLysS strain E. coli and affinity purified as previously described [15]. Purified SERA vinckei -1 was then electrophoresed on an SDS-PAGE gel, and CD-1 mice were immunized intraperitoneally with 50 -100 vg of the protein in gel slices as previously described [20].…”

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confidence: 99%

Plasmodial serine repeat antigen homologues with properties of schizont cysteine proteases

Gor

Wiser

et al. 1998

Molecular and Biochemical Parasitology

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Proteases appear to be required for critical events in the erythrocytic life cycle of malaria parasites, including the rupture of erythrocytes by mature schizonts and the subsequent invasion of erythrocytes by daughter merozoites [1,2]. This conclusion is supported by studies showing that parasite rupture and invasion of erythrocytes are inhibited by serine and cysteine protease inhibitors [1] and that the proteolytic processing of late schizont-stage proteins is required for the completion of the erythrocytic cycle [3,4]. A number of schizont protease activities have been identified biochemically [2], but limitations on available quantities of protein have made it difficult to definitively characterize these proteases or to ascertain their specific biological roles.The Plasmodium falciparum serine repeat antigen (known as SERA, SERA-1, SERP or P126 [5][6][7]) is being studied as a potential vaccine component [8]. A number of SERA homologues have been described, namely serine repeat protein homologue (SERPH [9] or SERA-2 [10]) and SERA-3 [10] from P. falciparum and five homologues from Plasmodium 6i6ax [11]. SERA and SERPH have been localized to the parasitophorous vacuole of mature schizonts [9,12], and SERA fragments are released into the bloodstream near the time of erythrocyte rupture [12]. SERA and its homologues all contain a 30 kDa 'protease domain' that has similarity in sequence to papain-family cysteine proteases, particularly near highly conserved active site residues [13] (Fig. 1A). Taken together, available data suggest that SERA and SERPH may act as late schizontAbbre6iations: SERA, serine repeat antigen; SERPH, serine repeat antigen homologue.

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Protective immune responses against protease-like antigens of the murine malaria parasite Plasmodium vinckei

Cited by 11 publications

References 40 publications

A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

A Subset of Plasmodium falciparum SERA Genes Are Expressed and Appear to Play an Important Role in the Erythrocytic Cycle

Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

Plasmodial serine repeat antigen homologues with properties of schizont cysteine proteases

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