The Pathogenesis of Foot-and-Mouth Disease in Pigs

Abstract

The greatest proportion 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 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 to predict outcomes of infection or vaccination in pigs. Furthermore, it has been shown that failure to account for these differences may have substantial 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 efficiency of transmission may vary depending on virus strain and exposure intensity. Multiple investigations have demonstrated that physical separation of pigs is sufficient to prevent virus transmission under experimental conditions. Detailed pathogenesis studies have recently demonstrated that specialized 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 infection results in modulation of several components of the host immune response. The infection is ultimately cleared in association with 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 are discussed in relation to specific pathogenesis events and the likelihood of transmission. Additionally, relevant aspects of the host immune response are discussed within contexts of conventional and novel intervention strategies of vaccination and immunomodulation.

Transmission of Foot-and-Mouth Disease Virus during the Incubation Period in Pigs

“…This is consistent with the concept that direct contact exposure, albeit of limited duration, is a highly stringent challenge system for FMDV studies in pigs [reviewed in Ref. (46)].…”

Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication

“…L pro and 3C ro are multifunctional proteins. In addition to the vital roles in processing of the polyprotein precursor, it is well-known that L pro and 3C ro are significantly involved in the viral antagonistic activity against host antiviral responses (Lawrence et al, 2012;Liu et al, 2015;Stenfeldt et al, 2016).…”

Foot-and-Mouth Disease Virus Capsid Protein VP1 Interacts with Host Ribosomal Protein SA To Maintain Activation of the MAPK Signal Pathway and Promote Virus Replication

“…MAPKs are important regulators of inflammatory cytokine and chemokine expression, and many viruses have been shown to exploit MAPK signaling by causing excessive inflammation for their own replication (20,28,35). Excessive inflammatory response has been associated with FMDV-induced diseases (36)(37)(38). A recent study reported that in evolved BHK-21 cell lines that were insensitive to FMDV infection, the MAPK signaling was weaker than in wild-type BHK-21 cells, suggesting that the decreased MAPK signaling may contribute to the resistance of cells to FMDV infection (39).…”