Roadmap for the research to underpin the development of control strategies for FMD

What are we trying to achieve and why? What is the problem we are trying to solve?

To elucidate FMD host-pathogen-environment interactions

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

• Identify virus-host protein-protein interactions (systematic and comprehensive).
• Increase knowledge of the functions of FMDV proteins including interaction with host factors.
• Investigate the role of microbiome on FMDV response and impact.
• Define strain specificity of virulence including SATs.
• Identify of factors defining cellular tropism.
• Define the role of RNA structure (coding and non-coding regions).
• Determine the role of cellular innate immune responses in FMDV infection of cattle and swine.
• Develop a reproducible FMDV challenge method in swine.
• Study virus life-cycle at animal population´s level (e.g. how can virus genomic diversity influence pathogenesis).
• Investigate serotype-host preferences
• Assess establishment and longevity of memory responses, importance of CMI.
• Integrate environmental variables- host species.
• Determine FMDV immune evasion mechanisms (is diversity a virulence factor?).
• Big data integration (i.e. for interactions with the environment).
• Multi-disciplinary data analysis (i.e. for interactions with the environment).

What approaches could/should be taken to address the research question?

In order to fully gain control of FMDV countermeasures development, a systematic and comprehensive genome-wide approach should be applied to the functional genomics of FMDV.

What else needs to be done before we can solve this need?

• Check in vitro results in animal models: it is important to make a correlation between the cell cultures and animal models.
• Collaboration with endemic countries.

Existing knowledge including successes and failures

Though many aspects of the pathogenesis of FMD remain incompletely elucidated, it is clear that rapid systemic
dissemination with high titre viral replication and dysregulated host immune responses are central to the observed
pathological processes. In contrast to the well-defined role of humoral immune responses, the contribution of T-cellmediated responses to immunity and their role in the induction of protective B-cell responses to FMDV in the natural host species are poorly understood. Virulence is a phenotype influenced by a highly complex virus-host interaction, and produces different results during infection with very close isolates (same serotype, topotype, and even same isolate).