Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue virus
Autor(es): Luplertlop Natthanej, Surasombatpattana Pornapat, Patramool Sirilaksana, Dumas Emilie, Wasinpiyamongkol Ladawan, Saune Laure, Hamel Rodolphe, Bernard Eric, Sereno Denis, Thomas Frédéric, Piquemal David, Yssel Hans, Briant Laurence, Missé Dorothée
Resumo: The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on crosstalk between the virus - the immune system of its vector Aedes aegypti (Ae. aegypti). Infection of the mosquito's salivary gl-s by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary gl-s - salivary gl-s of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary gl-s strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD) - Toll signalling pathways, - that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598). Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, - the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV - anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV) -, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide.
Imprenta: PLoS Pathogens, v. 7, n. 1, p. e1001252, 2011
Identificador do objeto digital: 10.1371/journal.ppat.1001252
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Flaviviridae ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Immune response ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Dengue ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2011
