A partial deletion within foot-and-mouth disease virus non-structural protein 3A causes clinical attenuation in cattle but does not prevent subclinical infection

Deletions within the 3A coding region of foot-and-mouth disease virus (FMDV) are associated with decreased virulence in cattle; however, the mechanisms are unknown. We compared experimental infection of cattle with virulent FMDV O1Campos (O1Ca) and a mutant derivative (O1Ca∆3A) lacking residues 87-106 of 3A. Unexpectedly, primary infection of the nasopharyngeal mucosa was similar for both viruses. However, while O1Ca caused viremia and fulminant clinical disease, O1Ca∆3A infection was subclinical and aviremic. There were no differences in expression of anti-viral cytokines in nasopharyngeal tissues between the groups, suggesting attenuation by O1Ca∆3A was a consequence of reduced replication efficiency in bovine cells, rather than a difference in the host response. These results demonstrated that although deletion in 3A of FMDV confers a clinically attenuated phenotype in cattle, the deletion does not prevent subclinical infection. These findings have implications for field scenarios involving outbreaks with apparently host-limited strains of FMDV.