| Flaviviruses, including dengue virus, yellow fever virus, and West Nile virus, are among the most important and common vector-borne infectious diseases to public health throughout the tropic and subtropical world. Although they continue to expand their geographic range and human incidence continues to rise, little is known about the interactions between these viruses and their invertebrate hosts. Chapter 1 of this dissertation provides background on these three flaviviruses and discusses strategies for control. Chapter 2 presents results from proteomic analysis identifying differentially expressed proteins during flavivirus infection in insect in vivo and in vitro systems. Pathway and network analysis are used to identify several cellular pathways that may be important during viral replication in the arthropod host, and successful identification of known proteins and cellular pathways demonstrates the validity of our combined proteomic and transcriptional assays. In Chapter 3, we investigate apoptosis, one of the cellular processes identified in Chapter 2 as significant in mosquito responses to flavivirus infection, through in vivo use of siRNA to activate the RNAi pathway against specific genes resulting in transient gene knockout. This is the first use of siRNA in whole mosquitoes and the first direct demonstration that modulation of the apoptosis pathway directly effects the replication of flaviviruses in mosquitoes. Finally, in Chapter 4 differential distributions of Aedes aegypti, Ae. mediovittatus and other mosquitoes along an urban-rural and altitudinal gradient in San Juan, Puerto Rico are reported. Aedes species extensively overlapped in low density housing areas, which has implications for dengue persistence. Together these chapters expand current molecular and ecological knowledge concerning mosquito-borne flavivirus infections. Better control of flaviviruses will be achieved through limiting flavivirus infection in mosquitoes and targeting environments in which humans are at greatest risk. |
