title: Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-000, Brazil.
authors.forename: Bianca B
authors.initials: BB
authors.lastname: Kojin
authors.affiliation: Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-000, Brazil.
authors.forename: André Luis
authors.initials: AL
authors.lastname: Costa-da-Silva
authors.affiliation: Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-000, Brazil.
authors.forename: Ceres
authors.initials: C
authors.lastname: Maciel
authors.affiliation: BSL3+ Laboratory, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-900, Brazil.
authors.forename: Dayane Alves
authors.initials: DA
authors.lastname: Henriques
authors.affiliation: Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-000, Brazil.
authors.forename: Danilo O
authors.initials: DO
authors.lastname: Carvalho
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, 92697, USA.
authors.forename: Kelcie
authors.initials: K
authors.lastname: Martin
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, 92697, USA.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Marinotti
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, 92697, USA.|Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, 92697, USA.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: James
authors.affiliation: Laboratório de Biologia Molecular de Flavivirus, Instituto Oswaldo Cruz/FIOCRUZ, Manguinhos, RJ, 21040-360, Brazil.
authors.forename: Myrna C
authors.initials: MC
authors.lastname: Bonaldo
authors.affiliation: Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-000, Brazil. mcapurro@icb.usp.br.
authors.forename: Margareth Lara
authors.identifier: http://orcid.org/0000-0002-7480-2116
authors.initials: ML
authors.lastname: Capurro
mesh_terms: D000330:Aedes / Q000235:genetics / Q000469:parasitology*; D000818:Animals; D002448:Cell Adhesion; D005260:Female; D015870:Gene Expression; D010963:Plasmodium falciparum / Q000502:physiology*; D010964:Plasmodium gallinaceum / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000469:parasitology; D034101:Sporozoites / Q000502:physiology*; D019076:Transgenes
chemical_list: D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan
keywords: Aedes aegypti; Circumsporozoite protein; Plasmodium falciparum; Plasmodium gallinaceum; Sindbis virus; Transgenic mosquitoes