Project description:Mosquito saliva contains bioactive factors that enhance viral infection, with sialokinin identified as a key contributor to vascular leakage and viral spread in mice. Understanding effect of sialokinin on human moncoytes, the most important innate cells that responsible for the viral-induced inflammatory, will provide important insight to host-virus-vector interaction in arbovirus infection.
Project description:Mosquitoes transmit many flaviviruses of global public health significance. Efficient viral transmission to mammalian hosts requires mosquito salivary factors that modulate local host responses, such as recruitment of virus-permissive myeloid cells to the bite sites. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown. Here, we showed that a female mosquito salivary gland-specific protein, named Aedes aegypti Neutrophil Recruitment Protein (AaNRP), acts as a key salivary component to facilitate the transmission of Zika (ZIKV) and dengue (DENV) viruses. AaNRP promotes a rapid influx of neutrophils followed by virus-susceptible myeloid cells toward mosquito bite sites, which facilitate establishment of local infection and systemic dissemination. Mechanistically, AaNRP engages TLR1 and TLR4 of skin resident macrophages and activates MyD88-dependent NF-κB signaling to induce the expression of neutrophil chemoattractants. Inhibition of MyD88-NF-κB with dietary resveratrol, a phytochemical, neutralizes the AaNRP effects, thus reducing flavivirus transmission by mosquitoes. This study offers mechanistic insight into saliva-aided viral transmission and provides a potential prophylactic target.
Project description:P. falciparum undergoes antigenic variation during its life cycle in the human host. To accomplish this, the malaria parasite has developed mechanisms that ensure the expression of a single member of the var gene family to produce one of the PfEMP1 variant proteins. Here we carry out RNA-seq and ChIP-seq analyses of histone modifications to explore transcriptional and epigenomic changes taking place between the transmissible stages of the parasite i.e. gametocytes present in human blood and sporozoites present in the mosquito salivary glands. We find that most var genes are expressed at low levels in gametocytes but a single var gene is selected during the oocyst stage in the mosquito. Clonal expression of a specific var gene is accompanied by the establishment of specific histone modification patterns in the active and inactive genes. These modifications are epigenetically transmitted from the oocyst to the infective sporozoite stage, where expression of the active var gene is amplified by the transcription of an antisense lncRNA. The findings suggest a critical role for the mosquito immune system in determining the choice of var gene activation prior to transmission to the human host.
Project description:Background: Anopheles culicifacies is a rural vector of malaria in tropical and sub tropical South East Asian region. The salivary gland of the mosquito is the target for sporozoite interaction, blood feeding behavior, haemostasis and vector-parasite interactions. Malaria parasite matures inside the salivary gland, gain competence and transmitted to the host along with the saliva during biting. The importance of the proteins expressed in salivary gland is the first step in understanding the physiology of blood feeding and may provide insights into vector- parasite interactions. Since, no genomic or transcriptomics information is available of Anopheles culicifacies, therefore locally expressed functional proteins in salivary glands are of much importance. . Method: In this study, 1DE protein and in solution digestion was combined with tandem mass spectrometry (nano LC-MS/MS) and computational bioinformatics for data mining was employed to study the proteome profile of salivary glands of sugar fed An. culicifacies mosquito species. Functional annotation of all the identified proteins was carried out using gene ontology tools, CELLO and SMART analysis software. Results: Total 102 proteins were identified and analysed by SEQUEST algorithm against mosquito protein database from Uniprot/NCBI. Out of which 81 proteins were identified using gel free approach and 21 proteins using in-gel approach and 15 were common among these two approaches. All the identified proteins were categorized in to 23 groups of biological processes using GO tool. 7 proteins were depicted to be secretary in nature by investigating the signal peptide present. Potential proteins with unknown function were predicted by analyzing their functional association with other characterized proteins by STRING algorithm and were categorized in cell adhesion, cytoskeleton and membrane trafficking networks. Conclusion: Our study elucidates the first proteomic dataset of An. culicifacies salivary gland proteins. Functional annotation of salivary proteins and complementary gene ontology assignments in An. culicifacies species may contribute towards understanding the complex physiology of the tissues in this species. This proteome baseline data may facilitate the discernment of salivary glands and parasite correlation during blood feeding. Furthermore, this mass spectrometry based proteomic data may also provide insights into the elucidation of role of differential functional proteins present in refractory An. culicifacies mosquito and may be useful for development of effective malaria control strategies.
Project description:Salivary glands are the only mosquito tissue invaded by Plasmodium sporozoites being a key stage for the effective parasite transmission and maturation, making knowledge regarding Anopheles sialome highly relevant to understand this process. In this study, we report for the first time a transcriptomic analysis using RNA-seq of An. gambiae infected by P. berghei.
Project description:To examine the effects of 20E treatment on mosquito gene expression, treated mosquito cells were examined by RNA-seq to determine the influence of 20E treatment.