Experimental foot-and-mouth disease in fattening pigs, sows and piglets in relation to outbreaks in the field

Donaldson, A.I.; Ferris, NP; Wells, GA

doi:10.1136/vr.115.20.509

Cited by 17 publications

(6 citation statements)

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“…However, there are sporadic reports of FMD outbreaks with unusually high mortality rates [[1],[2]], with fatalities often being attributed FMDV-associated myocarditis (as reviewed by [[3]]). Investigations based on specimens obtained from field outbreaks [[2],[4]], as well as experimental studies [[5],[6]], have confirmed a relationship between acute FMDV infection and fatal myocarditis in young ruminants and pigs.…”

Section: Introductionmentioning

confidence: 99%

Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

et al. 2014

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Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection. However, the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mononuclear inflammatory reaction, interstitial edema and cardiomyocyte degeneration in the myocardium of two pigs that died during acute infection with either of two different strains of FMDV. Despite similar clinical progression, there was a marked variation in morphological characteristics of myocarditis with a significant difference in intensity of myocardial inflammation between the two cases. Phenotypic characterization of leukocyte populations revealed that in both cases, the inflammatory infiltrate consisted mainly of combinations of CD172a+, CD163+ and CD44+ cells, with a distinct subset of CD8+ cells, but with consistent lack of detection of CD3+ and CD21+ cells. This suggests that the FMDV-associated acute myocardial inflammation in the two observed cases consisted mainly of leukocytes of monocyte lineage, with a distinct population of CD8+ cells which, based on lack of CD3 detection in serial sections, are likely to represent NK cells.

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Section: Introductionmentioning

confidence: 99%

Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

et al. 2014

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“…Death in young livestock, documented in calves, piglets and lambs, is a fairly common feature of FMD epizootics (Alexandersen & Mowat, 2005). Generally, the only gross pathological changes seen in these young animals are in the myocardium and death is often attributed to myocarditis (Donaldson et al , 1984; Gulbahar et al , 2007). In addition, the rare manifestation of FMDV-associated death in adults, known as ‘malignant FMD’, is characterized by lesions and degeneration of the myocardium (Arzt et al , 2011a; Shimshony et al , 1986).…”

Section: Introductionmentioning

confidence: 99%

Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity

Habiela

Seago

Pérez-Martín

et al. 2014

Journal of General Virology

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Laboratory animal models have provided valuable insight into foot-and-mouth disease virus (FMDV) pathogenesis in epidemiologically important target species. While not perfect, these models have delivered an accelerated time frame to characterize the immune responses in natural hosts and a platform to evaluate therapeutics and vaccine candidates at a reduced cost. Further expansion of these models in mice has allowed access to genetic mutations not available for target species, providing a powerful and versatile experimental system to interrogate the immune response to FMDV and to target more expensive studies in natural hosts. The purpose of this review is to describe commonly used FMDV infection models in laboratory animals and to cite examples of when these models have failed or successfully provided insight relevant for target species, with an emphasis on natural and vaccine-induced immunity. IntroductionFoot-and-mouth disease virus (FMDV: family Picornaviridae; genus Aphthovirus) is known to naturally infect a wide variety of cloven-hoofed domesticated and wild animal species, causing an acute disease characterized by vesicular lesions of the tongue, snout, buccal cavity, feet and teats (Grubman & Baxt, 2004). Despite causing extensive lesions, the cycle of infection in the individual animal is short, and foot-and-mouth disease (FMD) usually resolves without the need for treatment and is seldom lethal in adults (Arzt et al., 2011b). However, the highly contagious nature, wide dissemination and significant economic impact of FMD have made it one of the most feared livestock diseases and a major research focus for more than a century. Progress towards the development of effective tools for FMD control has been hampered by several factors including the cost and logistics of largeanimal experimentation in specialized high-containment facilities, incomplete knowledge of the host's immune systems and lack of immunological reagents compared to biomedical rodent species and humans. These factors delayed the production of vaccines on an industrial scale and this major research goal was subsequently only achieved in the 1950s (Lombard et al., 2007). In a review, Brown (2003) highlighted that this milestone could not have been achieved without certain significant advances in our knowledge of FMD. The first significant advance was the demonstration by Loeffler & Frosch (1897) that the disease was caused by a virus and the second was the establishment of FMD laboratory animal models, including the guinea-pig model (Waldman & Pape, 1920) followed by the suckling mouse model (Skinner, 1951). Although not without their flaws, these FMD laboratory animal models have helped elucidate several mechanisms of FMD pathogenesis, which would have been difficult to achieve directly in target species. These models have provided an accelerated time frame at significantly reduced costs to develop and test vaccine candidates and continue to be a useful tool for interrogating FMDV immune responses. However, we now know that porcine and ru...

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“…2 The virus can usually be isolated from myocardia in areas containing necrotic myocytes that are infiltrated with mononuclear cells. 13 FMDV binds to cells through a conserved Arg-Gly-Asp (RGD) sequence located in a flexible external loop between the bG and bH strands (G-H loop) of viral protein 1 (VP1). 18,32 The RGD is a recognition sequence for members of the integrin family of cell surface receptors.…”

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Myocarditis Associated with Foot-and-Mouth Disease Virus Type O in Lambs

et al. 2007

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The present study describes the pathogenetic mechanisms of myocarditis in 9 lambs that died in a foot-and-mouth disease outbreak in Samsun, Turkey. In all the heart samples tested, ELISA and sequencing for phylogenetic analyses showed that the virus, namely O/TUR/Samsun/05, was associated with the PanAsia pandemic strain of foot-and-mouth disease virus (FMDV) type O. The lambs had myocardial lesions but no typical vesicular lesions. In situ reverse transcription showed that many cardiomyocytes and some interstitial cells were positive for FMDV type O. Inflammatory infiltration, hyaline degeneration, and necrosis of sheets of myocytes were observed. The cellular infiltrates were mononuclear cells, including many lymphocytes, macrophages, a few plasma cells, and neutrophils. Major histocompatibility complex Class II+ dendritic and mononuclear cells, gammadelta T cells, CD172A+ and CD14+ macrophages and monocytes, and IgM+ B cells were detected mainly in the infected hearts. Inducible nitric oxide synthetase (iNOS) was seen mostly in areas of inflammation infiltrated by large numbers of cells. Of the 2 alpha-subunits of integrin known to be used as receptors by FMDV in epithelial tissues, CD49e (integrin alpha5) was detected in the membranes of cardiac myocytes with intercalated discs, but CD51 (integrin alphaV) was not detected in cardiac myocytes from infected or normal lambs. Interstitial and inflammatory cells were positive for both integrin subunits. The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)-positive signal was detected in the nuclei of both cardiac myocytes and interstitial cells from infected lambs. These findings suggest that the iNOS expressed by inflammatory cells in lesions may have a deleterious effect on cardiac myocytes in these lesions.

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Experimental foot-and-mouth disease in fattening pigs, sows and piglets in relation to outbreaks in the field

Cited by 17 publications

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Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity

Myocarditis Associated with Foot-and-Mouth Disease Virus Type O in Lambs

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