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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

ABSTRACT: Dengue viruses (DENV) are generally maintained in a cycle which requires horizontal transmission via their arthropod vector, Ae. Aegypti, to the vertebrate host. One important consequence of this process is the interference of these arboviruses with both invertebrate and vertebrate immune systems. While infection of vertebrates causes disease, the presence of DENV gives rise to life-long, persistent infection in mosquitoes. The results of a comparative transcriptome analysis between DENV-infected and uninfected salivary glands revealed activation of both the immune deficiency (IMD) and the Toll pathways, as well as involvement of the putative antibacterial cecropin-like peptide (AAEL000598), in controlling DENV infection in Ae. aegypti. The mature form of this peptide was found to be active against DENV and Chikungunya viruses, whereas its precursor also had a strong anti-Leishmania effect. This study is the first to establish a comparative transcriptome analysis of DENV-infected and uninfected salivary glands and demonstrates that certain DENV-induced peptides, that are part of the IMD pathway, possess broad-spectrum anti-pathogenic activity and may have therapeutic potential in human.

ORGANISM(S): Aedes aegypti

PROVIDER: GSE21528 | GEO | 2011/03/22

SECONDARY ACCESSION(S): PRJNA125945

REPOSITORIES: GEO

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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

Project description:Dengue viruses (DENV) are generally maintained in a cycle which requires horizontal transmission via their arthropod vector, Ae. Aegypti, to the vertebrate host. One important consequence of this process is the interference of these arboviruses with both invertebrate and vertebrate immune systems. While infection of vertebrates causes disease, the presence of DENV gives rise to life-long, persistent infection in mosquitoes. The results of a comparative transcriptome analysis between DENV-infected and uninfected salivary glands revealed activation of both the immune deficiency (IMD) and the Toll pathways, as well as involvement of the putative antibacterial cecropin-like peptide (AAEL000598), in controlling DENV infection in Ae. aegypti. The mature form of this peptide was found to be active against DENV and Chikungunya viruses, whereas its precursor also had a strong anti-Leishmania effect. This study is the first to establish a comparative transcriptome analysis of DENV-infected and uninfected salivary glands and demonstrates that certain DENV-induced peptides, that are part of the IMD pathway, possess broad-spectrum anti-pathogenic activity and may have therapeutic potential in human. Infectious blood meals were offered to 3-day-old, adult, female Ae. aegypti Liverpool mosquitoes using a silicone membrane feeder system (Alto et al., 2005). Human blood was combined with DENV-2 16681 to provide a blood meal titer of 5.106 plaque forming units (PFU)/ml. At different time-points after the blood meal, salivary glands were dissected in acid guanidium thiocyanate-phenol-chloroform (RNAble; Eurobio, France) or phosphate-buffered saline (PBS), and the samples were frozen at -70°C until use.

2011-03-21 | E-GEOD-21528 | biostudies-arrayexpress

Dengue virus inhibits immune responses in Aedes aegypti cells

Project description:The ability of many viruses to manipulate the host antiviral immune response often results in complex host-pathogen interactions. In order to study the interaction of dengue virus (DENV) with the Aedes aegypti immune response, we have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line Aag2. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a gram-negative bacteria species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology. Infected (dengue virus or heat-inactivated dengue virus) vs. naive cells. 3 replicates each.

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Post-transcriptional microRNA modifications in the Dengue mosquito vector, Aedes aegypti

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