Investigations upon the virus-host interaction of the bluetongue disease

• Applicant: Vanessa Herder, Ph.D.
• Subject Area: Veterinary Medical Science
• Term: from 2018 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406109949

Infections by the same pathogenic virus can result in variable clinical outcomes in different hosts, from subclinical infections to fatal disease, until now there is a lack of understanding the underlying mechanisms of such remarkable differences. Bluetongue is one of the major diseases of ruminants caused by Bluetongue virus (BTV), an arbovirus transmitted by biting midges. The clinical outcome of bluetongue in the infected host varies considerably between ruminants. BTV infected sheep ("susceptible" hosts) can show a severe, at times lethal, course of the disease while cows (“resilient” hosts), show only mild symptoms despite displaying high levels of viremia. This proposal aims to address a fundamental issue: how can a pathogenic virus make some infected hosts ill, while others display only mild or no disease (despite abundant virus replication in both hosts)? The clinical outcome of BTV infection will be evaluated in the context of the complex interplay between viral replication, the innate immune system, and the adaptive immune response of resilient (cows) and susceptible species (sheep). To reach this aim, it is planned to investigate the interferon system in experimentally BTV-infected cattle and sheep in order to characterize species differences as well as underlying molecular determinants. The interferon production of different cell types will be analysed on RNA and protein-level applying. The comparative analysis of gene expression will be evaluated by using RNA sequencing of endothelial cells in infected animals. Morphological changes in different organs of infected cows and sheep will be comparatively determined as well as viral replication, viremia, antibody-production and -specificity. Infection of the follicular dendritic cells of the regional lymph nodes during bluetongue disease and the loss of function of the cells represents a central goal of the study. Obtained results are always correlated with clinical data of both species. The first and second module of this study is comparatively examining the early phase of the infection focusing on BTV-infected cell types, viral replication and interferon production. In the second module, which also addresses the end of the early phase of BTV-infection, the mechanisms of virus-induced endothelial cell damage are analyzed. In the third module of the investigation the humoral immune response as well as morphologcial and molecular changes during the recovery phase of the disease are at the center of the investigation. This approach will allow us to dissect a naturally occurring arbovirus infection at an unprecedented scale by systematically correlating viral replication, adaptive and acquired immune response, pathology and clinical symptoms in two different species. In addition, this study will provide information on the extent to which the host interferon system during the early stages of infection influences the clinical course of arboviral infection.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Massimo Palmarini