Integrating molecular and structural biology techniques to identify capsid interactions and intermediates relevant to the early stages of Aphthovirus

ABSTRACT
Foot-and-mouth disease virus (FMDV) is a highly contagious member of the genus Aphthovirus which poses a major threat to cloven-hoofed animals such as cattle, pigs, and sheep, leading to substantial economic losses in agriculture globally. FMDV spreads rapidly through direct contact and aerosol transmission, necessitating the need for biosecurity measures in regions with outbreaks. Current vaccines based on inactivated FMDV particles exhibit limited stability, often leading to decreased efficacy. Consequently, an in-depth understanding of the structural and molecular biology of the dissociation of FMDV is critical for developing vaccines with improved robustness and longevity. Equine rhinitis A virus (ERAV), another Aphthovirus which causes respiratory infections in horses, is closely related to FMDV at both the nucleotide level and its physico-chemical properties. Due to these similarities, ERAV serves as a model for studying FMDV in lower containment laboratory settings. This proposal aims to elucidate the molecular mechanisms underpinning the initial stages of infection for both FMDV and ERAV. Employing a combination of molecular biology and structural biology approaches, we seek to identify and characterise key structural intermediates and capsid-receptor interactions that facilitate viral entry, genome release, and capsid disassembly. Insights into these processes will not only enhance our understanding of Aphthovirus biology but also inform the design of more stable and effective FMDV vaccines, potentially informing biosecurity strategies against this economically significant pathogen.
BBSRC THEMES
This project directly aligns with the BBSRC themes by advancing our understanding of the "rules of life" through the identification of interactions and intermediates of the Aphthovirus capsid. By elucidating the mechanisms that govern how the virus particle binds to its receptor and how viral genome is released from the endosome into the cytosol, it contributes fundamental knowledge to the biology of viral infections. Furthermore, the project supports "transformative technologies and biosciences for sustainable agriculture and food" by providing insights that could lead to the rational design of FMDV vaccines with improved stability and efficacy. Such advancements would be critical for controlling outbreaks and minimising the economic impact on livestock industries, thereby promoting more sustainable agricultural practices.