The pathogenesis of Foot-and-Mouth Disease in pigs

Authors: STENFELDT, CAROLINA - Oak Ridge Institute For Science And Education (ORISE); DIAZ-SAN SEGUNDO, FAYNA - University Of Connecticut; De Los Santos, Teresa; Rodriguez, Luis; Arzt, Jonathan

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2016
Publication Date: 5/23/2016
Citation: Stenfeldt, C., Diaz-San Segundo, F., De Los Santos, T.B., Rodriguez, L.L., Arzt, J. 2016. The pathogenesis of Foot-and-Mouth Disease in pigs. Frontiers in Veterinary Science. 3:41. doi: 10.3389/fvets.2016.00041.

Interpretive Summary: The greatest segment of foot-and-mouth disease (FMD) clinical research has focused on investigating disease mechanisms and improving vaccine protection in cattle. However, accumulated evidence from FMD outbreaks and experimental investigations suggest that there are several critical differences in disease mechanisms between pigs and cattle. It has also been shown that failure to account for these differences may have drastic consequences when FMD outbreaks occur in areas with dense pig populations. Recent experimental studies have confirmed that pigs are most susceptible to FMD virus (FMDV) infection via exposure of the upper gastrointestinal tract, and more resistant to infection through inhalation of virus. The infection spreads rapidly via direct contact between infected pigs, although several studies have shown that preventing physical contact between animals can prevent spread of infection amongst pigs housed in the same room. Detailed investigations have shown that the initial site of FMDV infection can be found in specialized epithelium within porcine oropharyngeal tonsils. During the clinical phase of infection, pigs shed large amounts of virus and are therefore a considerable source of contagion. The aim of this review is to provide an overview of knowledge gained from experimental investigations of FMD pathogenesis, transmission and host response in pigs. The progression of infection within individual animals and relevant aspects of the host immune response are discussed.

Technical Abstract: The greatest segment of foot-and-mouth disease (FMD) clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies that are specific to pigs. However, accumulated evidence from FMD outbreaks and experimental investigations suggest that critical components of FMD pathogenesis, immunology, and vaccinology cannot be extrapolated from investigations performed in cattle to explain or predict outcomes of infection or vaccination in pigs. Furthermore, it has been shown that failure to account for these differences may have drastic consequences when FMD outbreaks occur in areas with dense pig populations. Recent experimental studies have confirmed some aspects of conventional wisdom by demonstrating that pigs are more susceptible to FMD virus (FMDV) infection via exposure of the upper gastrointestinal tract (oropharynx) than through inhalation of virus. The infection spreads rapidly within groups of pigs that are housed together, although transmission rates may vary depending on virus strain and exposure intensity. Interestingly, multiple investigations have concluded that physical separation of pigs is sufficient to prevent virus transmission under experimental conditions. Detailed pathogenesis studies have demonstrated that specialized segments of epithelium within porcine oropharyngeal tonsils constitute the primary infection sites following simulated-natural virus exposure. Furthermore, epithelium of the tonsil of the soft palate supports substantial virus replication during the clinical phase of infection, thus providing large amounts of virus that can be shed into the environment. Due to massive amplification and shedding of virus, acutely infected pigs constitute a considerable source of contagion. FMDV modulates the host response by impairing several components of the innate immune response. The infection is ultimately cleared by a strong humoral response and, in contrast to ruminants, there is no subclinical persistence of FMDV in pigs. The aim of this review is to provide an overview of knowledge gained from experimental investigations of FMD pathogenesis, transmission and host response in pigs. Details of the temporo-anatomic progression of infection within individual animals is discussed in relation to specific pathogenesis events and the likelihood of transmission. Additionally, relevant aspects of the host immune response are discussed within the contexts of conventional and novel intervention strategies of vaccination and immunomodulation.