Induction of a Peptide with Activity against a Broad Spectrum of Pathogens in the Aedes aegypti Salivary Gland, following Infection with Dengue Virus

PLoS Pathogens

Dorothée Missé¹  Eric Bernard¹  Natthanej Luplertlop²  Ladawan Wasinpiyamongkol²  Laurence Briant³  David Piquemal⁴  Laure Saune⁵  Sirilaksana Patramool⁵  Rodolphe Hamel⁵  Pornapat Surasombatpattana⁵  Denis Sereno⁵  Frédéric Thomas⁵  Emilie Dumas⁵  Hans Yssel⁶ 

[1] Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), CNRS UMR 5236-UM1-UM2, Montpellier, France;Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Inserm, U844, Montpellier, France;Institut de Recherche en Biologie Végétale (IRV), Université de Montréal, Montreal, Quebec, Canada;Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 224 CNRS/IRD/UM1, Montpellier, France;University of Montpellier II, Montpellier, France

关键词: Salivary gl;    s;    Mosquitoes;    Immune response;    Dengue virus;    Gene expression;    Antibacterials;    Fats;    Aedes aegypti;   

DOI  :  10.1371/journal.ppat.1001252

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti). Infection of the mosquito's salivary glands 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 glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD) and Toll signalling pathways, and 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, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV) and, 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.

【 授权许可】

CC BY