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

Authors: STENFELDT, CAROLINA - University Of Minnesota; Arzt, Jonathan; PACHECO, JUAN - Former ARS Employee; Gladue, Douglas; Smoliga, George; SILVA, EDIANE - Oak Ridge Institute For Science And Education (ORISE); Rodriguez, Luis; Borca, Manuel

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2018
Publication Date: 1/12/2018
Citation: Stenfeldt, C., Arzt, J., Pacheco, J., Gladue, D.P., Smoliga, G.R., Silva, E., Rodriguez, L.L., Borca, M.V. 2018. A partial deletion within foot-and-mouth disease virus non-structural protein 3A causes clinical attenuation in cattle but does not prevent subclinical infection. Virology. 516:115-126. https://doi.org/10.1016/j.virol.2018.01.008.
DOI: https://doi.org/10.1016/j.virol.2018.01.008

Interpretive Summary: It is known that some strains of foot-and-mouth disease virus (FMDV) that are lacking certain regions of their genetic material are less virulent than viruses with an intact genome. However, the mechanisms responsible for these variations are not well known. In this study, cattle were infected with either an intact (“wild type”) version of FMDV, or a mutant that was missing a part of the genome that encodes for the protein known as 3A. Unexpectedly, there were no differences between the viruses with regards to the very early phase of infection during which the virus establishes infection in the upper respiratory tract. However, animals infected with the wild type virus went on to develop severe foot-and mouth disease, whereas animals infected with the mutant virus did not become sick. Although the animals that were infected with the mutant virus did not show any signs of disease, the virus was found in tissues of their upper respiratory tracts. These findings are important as they demonstrate that even though animals may not show clinical signs of disease, they may still be infected.

Technical Abstract: 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-delta3A) 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-delta3A 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-delta3A was a consequence of reduced replication efficiency in bovine cells, rather than a difference in the host response. These results demonstrated that although deletions in 3A of FMDV confers a clinically attenuated phenotype in cattle, the deletion does not prevent primary or persistent infection. These findings have implications for field scenarios involving outbreaks with apparently host-limited strains of FMDV.