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

Autor(es)

Kojin, Bianca B. ^[1] ; Costa-da-Silva, Andre Luis ^[1] ; Maciel, Ceres ^[1] ; Henriques, Dayane Alves ^[2] ; Carvalho, Danilo O. ^[1] ; Martin, Kelcie ^[3] ; Marinotti, Osvaldo ^[3] ; James, Anthony A. ^{[3, 4]} ; Bonaldo, Myrna C. ^[5] ; Capurro, Margareth Lara ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Lab Mosquitos Geneticamente Modificados, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Lab BSL3, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 - USA

^[4] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 - USA

^[5] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Mol Flavivirus, BR-21040360 Manguinho, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Malaria Journal; v. 15, MAR 10 2016.
• Citações Web of Science: 4

Resumo

Background: The 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. Methods: Peptides 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. Results: Transient 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. Conclusion: These 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. (AU)

• Processo FAPESP: 00/12138-7 - Mosquitos geneticamente modificados: possíveis aplicações no controle da transmissão de malária e dengue
• Beneficiário: Margareth de Lara Capurro-Guimarães
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 04/00889-9 - Efeito de genes antiplasmodium em mosquitos transgênicos
• Beneficiário: Bianca Burini Kojin
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto