BioProject

Mosquito-borne viruses are an emerging threat significantly impacting human health and well-being. More...

Mosquito-borne viruses are an emerging threat significantly impacting human health and well-being. Epidemics of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) have spread explosively throughout the Americas creating a public health crisis. Worldwide an estimated 3.9 billion people, living within 120 different countries, are at risk. Current research has provided substantial insights into the immune genes and pathways that shape resistance to vector-borne viruses and has revealed many promising targets for genetic manipulation. Rigorous studies have demonstrated that mosquitoes elicit major transcriptional changes in response to flavivirus infection. These include differential regulation of genes involved in the RNA interference pathways, classical immune pathways (e.g. JAK-STAT, Toll), production and transport of energy, metabolism, and the production of noncoding RNAs and microRNAs. Despite these advances, we are only just beginning to understand the complexity underlying mosquito-pathogen interactions. Mosquito resistance to infection is a dynamic phenotype, which will depend not only on genetic factors, but also environmental factors. Of the environmental variables potentially affecting mosquito resistance, temperature will play a central role.Our previous work identified a panel of differentially expressed genes in Ae. aegypti midguts in relation to variation in ambient temperature and ZIKV infection. These data suggest that viral replication is limited at cool temperatures due to increased oxidative stress associated with delayed blood meal digestion and an upregulated innate immune environment. We also have preliminary data that suggest variation in ambient temperature directly impacts key components of the viral replication cycle. In the proposed work, we shall expand upon these data to experimentally parse out the relative effects of temperature variation on the mosquito-virus interaction by characterizing how cooler temperatures impact the dynamics of expression, alternative splicing, and critical aspects of viral biology Less...