Abstract
Culicoides biting midges are the biological vector for Bluetongue virus (BTV), the aetiological agent of bluetongue disease (BT) in ruminants. Like all other hematophagous arthropods, Culicoides midges secrete pharmacologically active saliva during the acquisition of a blood meal. This saliva acts to counteract the mammalian host blood coagulation and local immune responses that are initiated as a result of vector blood feeding. As shown for numerous other arthropod-pathogen systems, Culicoides saliva may play a role in BTV infection, beyond simple virus transmission during blood meal acquisition. The work of this thesis highlights for the first time, that Culicoides sonorensis saliva can enhance BTV infection and replication within bovine monocytes, most likely via a mechanism that influences the early stages of virus infection. Furthermore, the undertaken studies identify that the saliva of C. sonorensis naturally contains bacterial lipopolysaccharides (LPS), and suggest that this non-protein salivary component is likely responsible for the observed saliva induced enhancement of BTV infection and replication. C. sonorensis saliva induced modification of the bovine host cytokine response was also assessed in this thesis. The presence of saliva during BTV infection was shown to enhance the production of the immunomodulatory cytokine IL-10 and also reduce the BTV induced production of IFN- from PBMC cultures from some, but not all, cattle. Collectively the results of this thesis highlight the active properties of C. sonorensis saliva in the context of enhancing BTV infection and the complex relationships between BTV, Culicoides midges, their salivary material and the bovine host, indicating the continuing need to elucidate these multifaceted virus-vector-host interactions. Furthermore, the study of these interactions will enable a greater understanding of the underlying mechanisms of BTV pathogenesis thus leading to potential applications to novel methods of viral control.