Uncovering the biological drivers of Aedes aegypti vector competence - Brackney & Steven Abstract: Aedes aegypti mosquitoes are the primary vector for numerous arthropod-borne (arbo) viruses including dengue virus (DENV; Flaviviridae, Flavivirus), Zika virus (ZIKV; Flaviviridae, Flavivirus), chikungunya virus (CHIKV; Togaviridae, Alphavirus) and yellow fever virus (YFV; Flaviviridae, Flavivirus). These arboviruses present a continued threat to human health worldwide with therapeutics and vaccines remaining limited. Further, traditional mosquito control measures have failed to reduce human disease risk and thus, novel control strategies are urgently needed. Gaining a better understanding of the factors mediating Ae. aegypti competency for these viruses could lead to novel interventions targeting critical processes within the system. Vector competence is the ability of an arthropod vector to acquire a pathogen, permit replication, and ultimately transmit the pathogen to a new host. Aedes aegypti competency for DENV is a quantitative trait influenced by many biotic and abiotic factors, yet the relative contribution that each biotic factor has on mediating infection is unknown. In this application, we are proposing to systematically test the relative contributions that host genetics, viral genotype, and microbiome composition have on vector competence variability. This is significant because understanding the influence that each of these factors has on conditioning infection will be essential to the development of novel interventions targeting critical processes within the system and allow for standardization across vector competence studies.