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Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue Virus.

Luplertlop N, Surasombatpattana P, Patramool S, Dumas E, Wasinpiyamongkol L, Saune L, Hamel R, Bernard E, Sereno D, Thomas F, Piquemal D, Yssel H, Briant L, Missé D - PLoS Pathog. (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

ABSTRACT
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.

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Related in: MedlinePlus

Leishmanicidal activity of GK and MK.The effect of MK (circles), MT (squares), and GK (triangles) peptides on the luciferase gene-containing promastigotes (A) L. infantum and (B) L. braziliensis was determined after 72 h of exposure of the parasites to various concentrations of the peptides. Untreated cultures correspond to parasite growing in culture medium only. The RLU percentage was calculated for each test sample according to the following formula [RLU in treated wells/RLU in untreated cultures]×100. Results represent mean values ± SD of three independent experiments.
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ppat-1001252-g007: Leishmanicidal activity of GK and MK.The effect of MK (circles), MT (squares), and GK (triangles) peptides on the luciferase gene-containing promastigotes (A) L. infantum and (B) L. braziliensis was determined after 72 h of exposure of the parasites to various concentrations of the peptides. Untreated cultures correspond to parasite growing in culture medium only. The RLU percentage was calculated for each test sample according to the following formula [RLU in treated wells/RLU in untreated cultures]×100. Results represent mean values ± SD of three independent experiments.

Mentions: Finally, in order to determine the spectrum of anti-pathogenic activity of the GK and MK peptides, their capacity to kill the human protozoan parasites L. infantum and L. braziliensis promastigotes, was evaluated as well (Figure 7). Of note, whereas the MK peptide mediated potent activity against both parasites with respective IC50 values of ∼15 µM (Figure 7A) and ∼10 µM (Figure 7B), the GK and the MT control peptides were inactive.


Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue Virus.

Luplertlop N, Surasombatpattana P, Patramool S, Dumas E, Wasinpiyamongkol L, Saune L, Hamel R, Bernard E, Sereno D, Thomas F, Piquemal D, Yssel H, Briant L, Missé D - PLoS Pathog. (2011)

Leishmanicidal activity of GK and MK.The effect of MK (circles), MT (squares), and GK (triangles) peptides on the luciferase gene-containing promastigotes (A) L. infantum and (B) L. braziliensis was determined after 72 h of exposure of the parasites to various concentrations of the peptides. Untreated cultures correspond to parasite growing in culture medium only. The RLU percentage was calculated for each test sample according to the following formula [RLU in treated wells/RLU in untreated cultures]×100. Results represent mean values ± SD of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3020927&req=5

ppat-1001252-g007: Leishmanicidal activity of GK and MK.The effect of MK (circles), MT (squares), and GK (triangles) peptides on the luciferase gene-containing promastigotes (A) L. infantum and (B) L. braziliensis was determined after 72 h of exposure of the parasites to various concentrations of the peptides. Untreated cultures correspond to parasite growing in culture medium only. The RLU percentage was calculated for each test sample according to the following formula [RLU in treated wells/RLU in untreated cultures]×100. Results represent mean values ± SD of three independent experiments.
Mentions: Finally, in order to determine the spectrum of anti-pathogenic activity of the GK and MK peptides, their capacity to kill the human protozoan parasites L. infantum and L. braziliensis promastigotes, was evaluated as well (Figure 7). Of note, whereas the MK peptide mediated potent activity against both parasites with respective IC50 values of ∼15 µM (Figure 7A) and ∼10 µM (Figure 7B), the GK and the MT control peptides were inactive.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus