Abstract
Foot-and-mouth disease (FMD) is the most devastating disease of cloven-hoofed livestock, with a crippling economic burden in endemic areas and immense costs associated with outbreaks in free countries. Foot-and-mouth disease virus (FMDV), a picornavirus, will spread rapidly in naïve populations, reaching morbidity rates of up to 100% in cattle. Even after recovery, over 50% of cattle remain subclinically infected and infectious virus can be recovered from the nasopharynx. The pathogen and host factors that contribute to FMDV persistence are currently not understood. Using for the first time primary bovine soft palate multilayers in combination with proteogenomics, we analyzed the transcriptional responses during acute and persistent FMDV infection. During the acute phase viral RNA and protein was detectable in large quantities and in response hundreds of interferon-stimulated genes (ISG) were overexpressed, mediating antiviral activity and apoptosis. Although the number of pro-apoptotic ISGs and the extent of their regulation decreased during persistence, some ISGs with antiviral activity were still highly expressed at that stage. This indicates a long-lasting but ultimately ineffective stimulation of ISGs during FMDV persistence. Furthermore, downregulation of relevant genes suggests an interference with the extracellular matrix that may contribute to the skewed virus-host equilibrium in soft palate epithelial cells.
Highlights
Foot-and-mouth disease (FMD) is an acute and severe systemic vesicular disease of cloven-hoofed animals (Artiodactyla) with tremendous economic impact
Infection with foot-and-mouth disease virus (FMDV) at low multiplicity of infection (MOI) resulted in limited cytopathic effect, high viral loads and presence of detectable viral antigen
After 28 dpi, the multilayers were still intact, but FMDV antigen and genome remained detectable at very low levels and viable virus could be isolated—giving a clear indication of FMDV persistence
Summary
Foot-and-mouth disease (FMD) is an acute and severe systemic vesicular disease of cloven-hoofed animals (Artiodactyla) with tremendous economic impact. The etiological agent is foot-and-mouth disease virus (FMDV), the type species of the genus Aphthovirus in the family. FMD mainly affects livestock such as cattle, buffalo, pigs, goats, and sheep, but can be transmitted to deer and wild boar. It is endemic in wild buffalo in Southern Africa [4,5]. More than 70 species are known to be susceptible to FMDV, its primary host seem to be buffalo and cattle, in which the disease causes very high morbidity, but only low mortality in adults [6]. During the onset of acute infection, cattle are highly febrile and small vesicles develop on the mucosal membranes of the muzzle, lips, and oral cavity, as well as on the coronary band and interdigital space, and the teats of the udder
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