Location: Foreign Animal Disease ResearchTitle: Pathogenesis of virulent and attenuated foot and mouth disease virus in cattle Author
|Pacheco Tobin, Juan|
|Stenfeldt, Carolina - Oak Ridge Institute For Science And Education (ORISE)|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2017
Publication Date: 5/2/2017
Citation: Arzt, J., Pacheco Tobin, J., Stenfeldt, C., Rodriguez, L.L. 2017. Pathogenesis of virulent and attenuated foot and mouth disease virus in cattle. Virology. 14(1):89. doi: 10.1186/s12985-017-0758-9.
Interpretive Summary: The continuum of attenuation and virulence of foot and mouth disease virus (FMDV; genus Aphthovirus family Picornaviridae) has been investigated in several studies, and multiple molecular determinants of virulence have been characterized. However, the critical mechanisms which define the establishment of systemic disease remain incompletely elucidated. Understanding these mechanisms is important as improved knowledge of the functional genomics of FMDV may contribute towards improved FMD control and eradication through development of next-generation countermeasures such as live-attenuated vaccines.
Technical Abstract: The factors defining virulence of foot-and-mouth disease virus (FMDV) in cattle were investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). After simulated-natural, aerosol inoculation, both viruses established primary infection in the nasopharyngeal mucosa with subsequent dissemination to the lungs. Immunomicroscopic localization indicated that both viruses infected epithelial cells within the nasopharynx and lungs as has been described for other strains of FMDV. The critical differences between the two viruses were a more rapid establishment of infection by FMDV-WT and quantitatively greater virus loads in secretions and infected tissues compared to FMDV-Mut. The slower replicating FMDV-Mut established a subclinical infection that was limited to respiratory epithelial sites, whereas the more prolific replication of FMDV-WT facilitated establishment of viremia and systemic dissemination of infection. Thus, under the current conditions, the virulent (FMDV-WT) phenotype was associated with viral dynamics of greater magnitude, which overcame containment of the host immune system and caused fulminant FMD.