Objective:
1: Develop a defined model to identify early (pre-viremic) events in the pathogenesis of FMDV in its natural hosts. 2: Develop tools to evaluate host-pathogen interactions at the genomics level. 3: Identify critical FMDV virulence determinants associated with mechanisms of invasion, infection, replication, persistence and transmission. 4: Understand the mechanisms of FMDV persistence and the viral carrier state in animals. 5: Determine mechanisms of FMDV interference with host responses.

Approach:
1: A defined model will be accomplished by developing and validating an inoculation model that mimics natural FMDV infections in target hosts. 2: Development of tools to evaluate the host-pathogen interaction will be accomplished through the design and development of a whole genome bovine microarray. 3: Identification of virulence determinants will be accomplished by: a.) Developing molecular tools to assess viral virulence factors. b.) Identify molecular events during FMDV-receptor interactions. c.) Identify components of the FMDV replication complex and the role of viral NSPs (non-structural proteins) in virus replication. d.) Determine the function of the FMDV 5' and 3' untranslated regions. 4: An understanding of FMDV persistence in the carrier state will be accomplished by: a.) Establishment and characterization of persistently infected cells. b.) Characterization of virus released from persistently infected cells. c.) Determine the role of autophagy in persistent infection. 5: Determination of FMDV interfernce with host responses will be completed by: a.) Examining the interference with the innate response in FMDV-infected cells. b.) Examining the mechanisms of FMDV immune evasion. BSL certifcation is pending.