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

被引：142

作者：

Luplertlop, Natthanej ^{[1
]}

Surasombatpattana, Pornapat ^{[2
]}

Patramool, Sirilaksana ^{[2
]}

Dumas, Emilie ^{[2
]}

Wasinpiyamongkol, Ladawan ^{[1
]}

Saune, Laure ^{[2
]}

Hamel, Rodolphe ^{[2
]}

Bernard, Eric ^{[3
]}

Sereno, Denis ^{[2
]}

Thomas, Frederic ^{[2
,4
]}

Piquemal, David ^{[5
]}

Yssel, Hans ^{[6
]}

Briant, Laurence ^{[3
]}

Misse, Dorothee ^{[2
]}

机构：

[1] Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok, Thailand

[2] UMR 224 CNRS IRD UM1, Lab Malad Infect & Vecteurs Ecol Genet Evolut Con, Montpellier, France

[3] CNRS UMR 5236 UM1 UM2, Ctr Etud Agents Pathogenes & Biotechnol Sante CPB, Montpellier, France

[4] Univ Montreal, Inst Rech Biol Vegetale IRV, Montreal, PQ, Canada

[5] Univ Montpellier 2, Montpellier, France

[6] INSERM, U844, Montpellier, France

来源：

PLOS PATHOGENS | 2011年 / 7卷 / 01期

关键词：

IMMUNE-RESPONSE; ANTIMICROBIAL PEPTIDES; CECROPIN; MELITTIN; GENE; TRANSCRIPTOMES; ACTIVATION; PATHWAY; GENOME; RELISH;

D O I：

10.1371/journal.ppat.1001252

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

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.

引用

页数：15

共 57 条

[1] Isolation, characterization and molecular cloning of new temporins from the skin of the North African ranid Pelophylax saharica [J].