The Orbivirus research group studies the pathogenesis and innate and adaptive immune responses of orbivirus infections in their mammalian hosts. Culicoides (biting midges) transmitted orbiviruses, such as bluetongue virus (BTV), represent highly important arthropod-borne viruses (arboviruses) of livestock both economically and in regards to their animal welfare impact. A unique aspect of arbovirus transmission is the specific and complex series of interactions between the virus and vector arthropod blood-feeding, facilitated by arthropod saliva.
Understanding the immune response of mammalian hosts towards arboviruses as well as to vector blood-feeding and saliva inoculation, is vital in fully understanding how these viruses cause disease, are transmitted and ultimately may be controlled. The research in our group is integrated into a wider research programme at The Pirbright Institute to investigate the mammalian host-virus-insect vector interaction of Culicoides-borne viruses, building on long established expertise of orbivirus research.
Several characteristics of BTV (and other orbiviruses) present great challenges to infection prevention and control. Our research aims to enhance critical knowledge on orbivirus pathogenesis and transmission allowing targeted control measures based on transmission disruption, better vaccine design (including cross-serotype protection) and potential treatment of valuable individual animals.
Specific current aims include:
- Identify ruminant immune responses to BTV which control viral infection and induce subsequent immune protection. Determine if immune-pathogenic mechanisms could contribute to disease manifestation in some host species
- Identify host or viral factors that drive virulence of certain BTV strains and the variation in clinical severity across different host species
- Analyse the local and systemic immune responses of mammalian hosts to Culicoides blood-feeding and saliva
- Determine the role of Culicoides blood-feeding and saliva for the subsequent dissemination, infectivity and virulence of arboviruses of livestock.
Current research in this group is funded by the Biotechnology and Biological Research Council (BBSRC), the EU, DEFRA as well as BBSRC and The Pirbright Institute funded studentships. Research projects currently carried out or about to commence are centred around the following themes.
- Virus and host factors driving BTV virulence and transmission: The severity of disease manifestation in vertebrate hosts following viral infections is determined by a combination of virus and host factors. Infections with orbiviruses such as BTV lead to severe haemorrhagic disease in some mammalian host species and asymptomatic infection in others. Our research aims to identify mechanisms resulting in such clinical differences by investigating if these viruses infect target cells with varying efficiency in different host species or if e.g. sheep and cattle activate distinct anti-viral responses. At least 27 serotypes of BTV have already been recognised, however virus strains belonging to the same serotype can greatly vary in their capability to spread and/or cause disease even in highly susceptible hosts. We will further investigate the genetic basis of viral traits such as virulence and transmissibility at the virus-vector-host interphase.
- Anti-viral responses to BTV infection in ruminant hosts: The current knowledge of ruminant immune responses to BTV infection remains superficial. Our research projects range from investigating anti-viral responses of natural target cells towards BTV to cell mediated immunity in the mammalian hosts. We specifically focus on the role of T lymphocytes in the pathogenesis, transmission and immune protection of BTV infection in sheep.
- The role of Culicoides blood-feeding and/or saliva on virus infectivity and transmissibility: Our research is specifically targeted at the unique interaction between the virus, Culicoides saliva and the mammalian host response following blood-feeding and virus infection. The saliva of arthropods contains a vast range of pharmacologically active molecules, which inoculated into mammalian skin often lead to inflammatory host responses, including the induction of hypersensitivity. We currently investigate the local and systemic mammalian immune responses towards Culicoides blood feeding and if these could be exploited for Culicoides control or virus transmission disruption. Furthermore we are studying how BTV particle modification by Culicoides saliva proteases changes viral particle cell entry, dissemination and infectivity across numerous viral strains.
The group is additionally involved in collaborative projects on arbovirus biological and mechanical transmission, molecular diagnostics of orbivirus infections and outbreak responses to orbivirus incursions as well as viral sharing across species barriers.
Our studies will enhance critical knowledge on orbivirus pathogenesis and transmission, aiming to design targeted control measures based on transmission disruption, better vaccine design (including cross-serotype protection) and potential treatment of valuable individual animals. Furthermore, our research of immune responses to arboviruses in natural host systems in the context of insect blood feeding and saliva co-inoculation will further contribute to the wider understanding of other arbovirus-vector systems including those of relevance to human health.