Project description:Flaviviruses pose growing global health threats and are transmitted by Aedes mosquitoes. Yet, how these viruses overcome early mosquito immunity remains unclear. Here, we reveal a cross-host immune evasion strategy in which the flavivirus NS1 protein, abundantly secreted into infected human serum, is taken up by mosquitoes during blood feeding and rapidly internalized into midgut epithelial cells—prior to viral replication. NS1 hijacks the mosquito spliceosome-associated factor Prp19 to promote miR-275-5p maturation, which suppresses the caspase gene CASPS19, blocking apoptosis and enabling early viral replication. Engineered mosquitoes expressing a miR-275 sponge show enhanced resistance to dengue and Zika viruses. These findings uncover a previously unrecognized mechanism whereby a vertebrate-derived viral protein reprograms vector gene regulation, establishing a new paradigm of cross-species immune manipulation by flaviviruses.
Project description:Metagenome data from soil samples were collected at 0 to 10cm deep from 2 avocado orchards in Channybearup, Western Australia, in 2024. Amplicon sequence variant (ASV) tables were constructed based on the DADA2 pipeline with default parameters.
Project description:Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, depends on the availablity of a high-quality genome assembly. Here we use DNA proximity ligaton (Hi-C) and Pacific Biosciences long reads to create AaegL5 - a highly contiguous A. aegypti reference.
Project description:Mosquitoes serve as medically significant vectors for transmitting various arboviruses. The mosquito midgut is both the digestive organ and primary infection site via viral bloodmeals, and the midgut cells show heterogeneity on virus-vector interactions. Rapidly developed single-cell RNA sequencing (scRNA-seq) technologies allow to characterize midgut physiology and viral infection dynamics at cellular solution. At present, scRNA-seq studies about mosquito midgut cell atlas are still limited and lack established protocols for cellular isolation. Therefore, we developed and employed a compatible microwell-based scRNA-seq protocol on four important mosquito species including Aedes aegypti, Aedes albopictus, Culex pipiens pallens and Culex tritaeniorhynchus and successfully established their midgut cell atlases pre- and post-bloodmeal. Further, we performed scRNA-seq experiments on DENV-infected Ae. aegypti to characterize the viral infection dynamics at single-cell solution.
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.
