Towards a better understanding of foot-and-mouth disease

The imaging of vanishingly tiny structures created by the foot-and-mouth disease virus could one day help scientists develop new treatments for infected animals. 

In a new study published today, biologists from the University of Leeds, in collaboration with colleagues at the University of Glasgow Centre for Virus Research, observed the interaction between components of the virus in test tube experiments under bio-secure conditions.  

The image reveals the formation of tube-like structures called fibrils which emerged when the components were mixed in vitro and began to replicate. 

But when the proteins were manipulated to prevent the virus genome replicating, the fibrils did not form. 

The scientists behind the discovery concluded that these fibrils could play a key role in the virus’s ability to replicate, a highly complex process that is not fully understood.  

The findings could lead to further developments in treatments for diseases caused by the virus. 

Senior author Dr Eleni-Anna Loundras, currently a Post-Doctoral Researcher at the Pirbright Institute, carried out the research as part of her PhD in Molecular and Cellular Biology in Leeds’s Faculty of Biological Science.  

She said: “These significant findings shed light on the key molecular interactions and dynamics involved within these complicated viral replication complexes, which we still have much to learn about. 

“This exciting model has helped us to observe regions that could be of interest to target for antiviral treatment.” 

In test-tube experiments, the researchers took foot-and-mouth disease virus proteins and observed the interactions under powerful electron microscopes at the University of Leeds Astbury Centre and the University of Glasgow Centre for Virus Research. They created high resolution images to visualise and model the fibril structures.  

Preventing the replication of the virus through protein manipulation also stopped production of fibrils, suggesting these structures play a key role in virus reproduction. 

Dr Loundras said: “Our research indicates that these fibrils have a function in viral replication in lab experiments, but we don’t yet know how important they are in a living cell. Further research into the function of these structures will be possible in years to come, as imaging technology improves.” 

Research supervisor Nicola Stonehouse, Professor of Molecular Biology in the University of Leeds’ School of Molecular and Cellular Biology, said: “The paper is the result of a really enjoyable collaboration between Leeds and Glasgow, and shows the impact of ‘team science’.” 

Further information 

Contact University of Leeds press officer Lauren Ballinger via l.ballinger@leeds.ac.uk with media enquiries. 

Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for genome replication is published in Communications Biology on 17 January 2022 

DOI: 10.1038/s42003-021-02989-z 

Picture: A close up of a fibril structure. Credit David Bhella, University of Glasgow 

Authors: 

Lead author: Eleni-Anna Loundras, University of Leeds 

Supervising author: Nicola J. Stonehouse, University of Leeds 

James Streetley, University of Glasgow 

Morgan R. Herod, University of Leeds 

Rebecca Thompson, University of Leeds 

Mark Harris, University of Leeds 

David Bhella, University of Glasgow