Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands

Malaria Journal

Research

Dayane Alves Henriques¹  Osvaldo Marinotti²  Kelcie Martin²  Anthony A. James³  Myrna C. Bonaldo⁴  Bianca B. Kojin⁵  Danilo O. Carvalho⁵  André Luis Costa-da-Silva⁵  Ceres Maciel⁵  Margareth Lara Capurro⁵ 

[1] BSL3+ Laboratory, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil;Department of Molecular Biology and Biochemistry, University of California Irvine, 92697, Irvine, CA, USA;Department of Molecular Biology and Biochemistry, University of California Irvine, 92697, Irvine, CA, USA;Department of Microbiology and Molecular Genetics, University of California, 92697, Irvine, CA, USA;Laboratório de Biologia Molecular de Flavivirus, Instituto Oswaldo Cruz/FIOCRUZ, 21040-360, Manguinhos, RJ, Brazil;Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-000, São Paulo, SP, Brazil;

关键词: Plasmodium gallinaceum;    Plasmodium falciparum;    Circumsporozoite protein;    Sindbis virus;    Transgenic mosquitoes;    Aedes aegypti;   

DOI  :  10.1186/s12936-016-1207-8

 received in 2015-09-05, accepted in 2016-03-01,  发布年份 2016

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Kojin et al. 2016