Abstract
BackgroundThe circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. Sporozoite invasion of mosquito salivary glands prior to transmission is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (NH2)-terminal portion of CSP is involved in this interaction but not the TSR region on the carboxyl (C)-terminus. Peptides based on the NH2-terminal domain could compete with the parasites for the salivary gland receptors and thus inhibit penetration.MethodsPeptides based on the NH2-terminus and TSR domains of the CSP from avian or human malaria parasites, Plasmodium gallinaceum and Plasmodium falciparum, respectively, were expressed endogenously in mosquito haemolymph using a transient (Sindbis virus-mediated) or stable (piggyBac-mediated transgenesis) system.ResultsTransient endogenous expression of partial NH2-terminus peptide from P. falciparum CSP in P. gallinaceum-infected Aedes aegypti resulted in a reduced number of sporozoites in the salivary glands. When a transgenic approach was used to express a partial CSP NH2-terminal domain from P. gallinaceum the number of sporozoites in the salivary glands did not show a difference when compared to controls. However, a significant difference could be observed when mosquitoes with a lower infection were analysed. The same result could not be observed with mosquitoes endogenously expressing peptides based on the TSR domain from either P. gallinaceum or P. falciparum.ConclusionThese results support the conclusion that CSP partial NH2-terminal domain can be endogenously expressed to promote a competition for the receptor used by sporozoites to invade salivary glands, and they could be used to block this interaction and reduce parasite transmission. The same effect cannot be obtained with peptides based on the TSR domain.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1207-8) contains supplementary material, which is available to authorized users.
Highlights
The circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans
Circumsporozoite binding protein (CSPBP) and saglin, were identified as receptors for sporozoites and these interact with the parasite-expressed circumsporozoite protein (CSP) and thrombospondin-related anonymous protein (TRAP), respectively [4, 5]
RT-PCR analyses verified that females injected intrathoracically with Sin-PfpNT, Sin-PgRTSR, Sin-PfRTSR, Sin-PgpTSR and the control Sin-EGFP viral particles were accumulating the respective transcripts on the 11th day post-viral infection, which is the day the P. gallinaceum challenge was performed (Fig. 2b)
Summary
The circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. CSP is the predominant sporozoite surface antigen and important for mediating recognition and invasion of the salivary glands (as reviewed [7, 8]) It is expressed by a single copy gene [9], and has a large central immunodominant domain comprising tandem repeats of small peptides. The carboxyl-(C) terminus, which has sequence similarity to the thrombospondin type-1 repeat (TSR) superfamily, has an 18-amino acid sequence (EWSXCXVTCGXG(V/I)XXRX(K/R) designated Region II [13,14,15], and a putative glycosylphosphatidylinositol (GPI) anchor attachment site. Both Regions I and II are conserved highly among Plasmodium species [16]
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