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. 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 viral and host factors that drive viral pathogenesis, disease manifestation.
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
- Determine the role of the different BTV particle types and viral variants on modifying infectivity within the wide range of natural host and vector target cells
- 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 and DEFRA. Research projects currently carried out are centred around the following themes:
- Virus and host factors driving BTV transmission and virulence: 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. We are currently investigating if BTV infection can modify the emission of volatile organic compounds within the body odour of sheep and/or cattle which might change the attraction of blood-feeding Culicoides and/or potentially allow the development of new diagnostic approaches. At least 28 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. Our research aims to identify mechanisms resulting in such clinical differences by investigating if these viruses (and the different existing virus particle types) infect target cells with varying efficiency. We are also investigating the genetic basis of viral traits such as virulence and transmissibility at the virus-vector-host interphase. The genome of orbiviruses consists of 10 dsRNA segments which can be exchanged when two strains infect the same cell in a process called reassortment and we are further determining the mechanisms and effects of genome reassortment on viral diversity and variant selection.
- 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 further elucidating adaptive immunity in the mammalian hosts. We specifically study the role of T lymphocytes in the pathogenesis, transmission and immune protection of BTV infection in sheep. Furthermore, we are comparing the dynamics and quality of anti-BTV immunoglobulins comparatively in cattle and 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. We are currently studying how BTV particle modification by Culicoides saliva proteases changes viral particle cell entry, dissemination and infectivity in a wide range of natural target cells 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.