Abstract
Elephant endotheliotropic herpesviruses (EEHVs) cause a fatal haemorrhagic disease (EEHV-HD) in juvenile Asian elephants (Elephas maximus) and pose the single greatest threat to the sustainability of this endangered species in captivity. Although supportive veterinary treatment improves prognoses, efficacious antiviral treatments and/or vaccination strategies are severely lacking. Therefore, focus is being placed on the role of the immune system in controlling EEHV infections. The peracute progression of disease suggests that only the innate immune system can respond fast enough to hinder viral replication, as seen for other herpesviruses and viral haemorrhagic fevers. This project therefore aimed to investigate the efficacy of veterinary immunostimulants in Asian elephants and the bioactivity of recombinant Asian elephant interferon proteins. Multiple key Asian elephant innate immune genes were identified and sequenced for the development of species-specific qRT-PCR assays. Subsequent gene expression analysis demonstrated significant upregulation for almost all genes tested within 24 hours of ex-vivo administration of two commercially available veterinary immunostimulant medications to whole Asian elephant blood. Additionally, sequence data produced for Asian elephant type I interferons was used to express recombinant interferon alpha and beta proteins which were then investigated for bioactivity in-vitro, relative to human interferons. Both human and elephant interferons provided full protection against bovine alphaherpesvirus 1, even when applied 24 hours post-infection. The evidence presented in this project therefore suggests that widely available immunostimulant and interferon medications may help control EEHV infections, lower EEHV-HD mortality and aid conservation efforts of this endangered species.