Understanding, forecasting, and mitigating zoonotic mosquito-borne viral disease in the U.K.

Effective surveillance and control of vector-borne disease (VBD) in the UK requires an integrative approach. This multi-disciplinary project combines diverse expertise from medical entomology, virology to computational modelling to investigate areas related to the understanding, forecasting, and mitigation of mosquito-borne disease in the UK. By forging partnerships across several institutions, we will address questions including (i) how and where local transmission will most likely occur; (ii) how can proven vector control strategies be adapted to a UK context; and (iii) and investigate novel approaches to mitigate risk. Our collaboration spans academic, industry, and governmental organisations, providing the unique capacity and expertise needed to address these questions. The first work package (WP) (led by Co-I Dr Jones and Co-I Dr Lord [Early Career Researcher - ECR]) will determine factors that influence the potential for transmission of WNV over a fine scale using field studies and computational modelling. This includes mosquito community composition in different habitats, movement between these habitats (Dr Chapman), and whether mosquito and bird communities have the capacity to sustain transmission (Dr Mason, STFC Hartree). Models of WNV transmission will then be used to determine the efficacy of control strategies in the context of these communities. Focusing on these fine-scale dynamics is important as this granularity may be overlooked in broad scale national surveys, and the questions raised here will inform on the usefulness and reliability of these surveys. In work package two (led by RCo-I Dr Longbottom [ECR] and Co-I Dr Lord [ECR]), we will produce species distribution maps for potential WNV vectors. Previous estimates are over 10 years old and additional contemporary spatial data has since become available. Additionally, this work package will explore different spatial scales for model prediction and accuracy and investigate the use of outputs of varying scales in policy and implementation. Elements of this work package will leverage partnerships at UKHSA to facilitate stakeholder discussion and research uptake. Collectively WP1 and 2 will build on existing WNV risk assessments to inform government policy, by providing fine-scale data and a focus on communities of mosquitoes rather than individual species. In the final work package, we will explore novel and proven vector control strategies for their applicability to the UK. In part A (led by PI Dr Hughes), we will partner with Verily Life Sciences and Dr Walker (University of Warwick) to develop a Wolbachia-based control strategy for Culex mosquitoes. We will introgress a novel Wolbachia strain into the Culex molestus background and examine its capacity to alter mosquito reproduction and suppress mosquito populations. Additionally, we will examine the ability of Wolbachia to block pathogens relevant to the UK including WNV and Usutu virus (USUV). Results from this work will form the basis of future control approaches and our partnership with Verily Life Sciences uniquely places us to rapidly transition this research into an applied control approach in the UK. In part B of this final work package (led by RCo-I Dr Casas-Sanchez), we will examine how glycosylation pathways affect arboviruses such as WNV and USUV in vitro and in vivo. The ability to block the virus, rather than target the mosquito enables vector control approaches that can work across mosquito species, a critical factor given the role of multi-species communities in transmission (identified in WP1). We have ECRs as work packages leads and we commit to mentoring these researchers in this project and more generally towards their independence. Together, our OneHealth approach and spectrum of understanding, forecasting, and mitigation of VBD will provide critical data for future planning and research as we move towards the aim of reducing the risk of transmission in the UK.

Autochthonous transmission of USUV was recorded in London in 2020 and in the last decade increasing numbers of human cases of WNV in Europe have occurred. Focussing on WNV, we will determine the conditions permitting onward transmission if introduced into the UK, by integrating field studies in medical entomology, ornithological data and stochastic, spatial transmission models. We will produce national species distribution and abundance maps for potential WNV vectors. By integrating these national-level analyses with forecasting fine-scale WNV transmission dynamics, we will determine how to best link information across spatial scales to target future surveillance strategies. Collectively, these activities will enable us to inform the quantitative risk assessments for WNV planned by our partners at the UKHSA. Improved understanding and forecasting of mosquito-borne virus risk are only useful if there are sufficient preparations made for mitigation in response. We will therefore explore the adaptation of existing and development of novel vector control strategies. This will involve the creation of a novel Wolbachia infection in Cx. molestus and characterisation of its capacity to suppress mosquito populations. We will also examine Wolbachia pathogen blocking in a Culex host background against WNV and USUV. In addition, we will determine the importance of protein glycosylation for WNV and USUV infection in both mosquito and vertebrate hosts and identify specific glycans required for cell invasion, and determine if the glycosylation approach is synergistic with Wolbachia blocking of pathogens. Alongside our in vivo pilot studies, this will provide a baseline for the development of modern control strategies which could also be used for other arboviruses. Together, our OneHealth approach will provide a thorough understanding of VBD in the UK and forecast risks. This will inform policy and develop mitigation strategies in preparation for future outbreaks.