Chronic bee paralysis virus: The epidemiology, evolution and mitigation of an emerging threat to honey bees.

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We will study the epidemiology and evolution of chronic bee paralysis virus (CBPV) which causes severe disease in honey bee colonies, with the purpose of working with industry to develop mitigation strategies. There are four objectives of this study:

- To gather new data on the disease dynamics using qRT PCR to monitor the temporal and spatial spread of CBPV in colonies and apiaries. We will use structural equation models and microsimulation models on new case-control data with five classes of potential stressor: The presence of pathogens (qPCR/RT PCR); pesticide exposure (using LC/MS-MS and GC/MS); prior weather (EDINA/MO); land use local to apiary; and apiary management (using beekeeper surveys). Where these classes contain multiple attributes, we will use multivariate approaches (Principal Components Analysis) to create composite variables for inclusion in the analysis.

- To investigate the role and importance virus evolution in the recent emergence of CBPV. We will sequence a range of historic and modern isolates using nanopore (MinION) sequencing, and develop reverse genetic systems to create infectious historical isolates and potential future reassortants. Transmissibility and virulence in honey bees and non-Apis pollinators will be assessed using controlled adult cage tests.

- To investigate, co-infection, poor weather and confinement, singularly and in combination as stressors of CBPV-disease. The impact of various combinations of stressors on transmissibility and virulence will be determined for different CBPV genotypes using controlled laboratory cage studies and survival analysis.

- Using data and simulation models, we will work with the BFA to develop and rigorously test management strategies using field trials on BFA apiaries, resulting in the development of a chronic paralysis management toolkit for apiarists.

Academic groups interested in honey bee health will be informed by the experiments to characterise the virus transmission pathways and the interactions between poor weather and coinfection. Methods developed to monitor shifts in transmission and virulence due to challenge with co-stressors will be useful for other better-studied pollinator diseases, where these data are largely absent. Our proposed work on non-Apis pollinators will extend interest to groups working on wild pollinator health - the interaction between pathogens in managed bees and wild pollinators is a rapidly advancing area of research. More generally, those interested in understanding the drivers behind emerging disease in complex biological systems could benefit from the biostatistical and simulation modelling frameworks developed. Our work will also elucidate the contribution of viral reassortants (for example, with segments derived from different genotypes of the virus) to transmission and virulence. These results will be of great interest to groups studying segmented viruses, which are associated with a wide range of diseases in humans, their livestock or plants. The development of a reverse genetic system for chronic bee paralysis virus will - for the first time - enable the detailed analysis of the structure and function of the bipartite virus genome. This development is, these days, a pre-requisite for the comprehensive analysis of any virus. The majority of the proteins (predicted or known) encoded by CBPV are of unknown function. Through a combination of sequence analysis to highlight conserved functional domains, and the development of strategies giving researchers the ability to 'knock out' proteins (reverse genetics), our studies will have a significant impact on the understanding of this poorly characterised virus.
Our key end-user groups are commercial and hobbyist beekeepers whose honey bee stocks are suffering with dramatically increasing levels of chronic paralysis with no clear intervention strategies to minimise disease impact. Our proposal has been developed in close collaboration with the Bee Farmers' Association (BFA) - who represent professional bee farmers from across the UK - to generate the necessary biological data to develop informed management practices. We will work with the BFA to translate research outcomes into rigorously tested programmes for the early detection and management of chronic paralysis. This 'management toolkit' will be distributed to BFA members and the amateur beekeeping sector through our extensive links with both groups, and through disease management workshops. Honey bee diseases are of considerable interest to the agrichemical companies, both large and small. Our data could highlight the need for new anti-viral interventions that would be of interest to these groups.
Policy makers will be interested to interpret the drivers of chronic paralysis emergence in honey bee populations, to see how our data might inform the delivery of key policies designed to protect pollinator populations. Government sponsored inspection and advisory services will benefit from having new information to share with beekeepers, to improve the impact of their activities and help reduce losses to this damaging disease.
Our results will be of interest to the general public, who keep a watchful eye on developments in pollinator health. The "plight of the honeybee" is regularly in news stories. We will use our experience as science communicators to raise awareness and appreciation of the science underpinning beekeeping and bee diseases, and to help distinguish between the hype and the reality of the current threats to honey bees and other pollinators.