UC Davis

Arthropod borne viral (Arboviral) disease accounts for 17% of the total infectious disease burden, afflicting over 100 million people annually. Global expansion of mosquito-borne arboviruses demands integrated approaches to vector control and public health surveillance. However, disparate outcomes in laboratory vector competence studies complicates risk assessment of mosquito species as vectors. While the contribution of mosquito and viral genetics has enjoyed much attention, the effects of mosquito microbiota on arboviral transmission potential are poorly understood. For Aedes aegypti, which is an effective vector for many arboviruses including Zika virus (ZIKV), the microbiota is primarily environmentally derived and dominantly resides in the gut. Chapter 1 reviews the current knowledge of Ae. aegypti vector competence for Zika virus as well as known effects that mosquito microbiota have on vector competence. Chapter 2 assesses the impact of microbes acquired from the larval habitat on Ae. aegypti development and ZIKV transmission. Adult female mosquitoes that emerged from microbially rich larval water derived from cemetery headstones were found to harbor more diverse microbiota and consistently lower ZIKV infection and transmission rates than their laboratory counterparts reared in laboratory tap water. However, microbial community compositions varied between experiments despite a consistent phenotype. Together, the results suggest that wild Ae. aegypti are likely less competent vectors than conventionally determined in the lab where larvae are typically reared in tap water, and that this effect is mediated by mosquito interactions with their microbiota. Chapter 3 investigates the reversibility of larval microbe-mediated refraction of ZIKV after developmental maturity. A higher dissemination rate was observed in Ae. aegypti depleted of gut microbes during pupation, and this was linked to reduced blood digestion efficiency. Results of this work suggest an immuno-metabolomic mechanism by which gut microbes confer resistance to ZIKV dissemination, by way of nonstructural midgut modifications. Overall, work presented in this dissertation emphasizes the importance of environmental microbes as a source of variation in infection susceptibility that demands consideration when conducting vector competence studies. It also highlights the complex interactions between mosquito, virus, and all the symbionts in between that play shape transmission out in nature.