Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems

Stenfeldt, Carolina; Pacheco, Juan M.; Singanallur, Nagendrakumar Balasubramanian; Ferreira, Helena Cardoso de Carvalho; Vosloo, Wilna; Rodrı́guez, Luis L.; Arzt, Jonathan

doi:10.1016/j.vetmic.2015.04.004

Cited by 14 publications

(23 citation statements)

References 32 publications

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“…Clinical signs of FMD in sheep are often described as mild or inapparent [4]. However, some studies have reported severe clinical FMD in experimentally infected sheep characterized by fever, marked lameness, and vesiculo-erosive lesions on the feet and in the oral cavity [5,6]. Additionally, FMD outbreaks may lead to substantial lamb mortality, which is generally attributed to FMDV-associated myocarditis [7,8].…”

Section: Introductionmentioning

confidence: 99%

Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep

et al. 2019

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Foot-and-mouth disease virus (FMDV) is capable of infecting all cloven-hoofed domestic livestock species, including cattle, pigs, goats, and sheep. However, in contrast to cattle and pigs, the pathogenesis of FMDV in small ruminants has been incompletely elucidated. The objective of the current investigation was to characterize tissue-and cellular tropism of early and late stages of FMDV infection in sheep following three different routes of simulated natural virus exposure. Extensive post-mortem harvest of tissue samples at predetermined time points during early infection (24 and 48 hours post infection) demonstrated that tissues specifically susceptible to primary FMDV infection included the paraepiglottic-and palatine tonsils, as well as the nasopharyngeal mucosa. Additionally, experimental aerosol inoculation of sheep led to substantial virus replication in the lungs at 24-48 hours post-inoculation. During persistent infection (35 days post infection), the paraepiglottic-and palatine tonsils were the only tissues from which infectious FMDV was recovered. This is strikingly different from cattle, in which persistent FMDV infection has consistently been located to the nasopharyngeal mucosa. Analysis of tissue sections by immunomicroscopy revealed a strict epithelial tropism during both early and late phases of infection as FMDV was consistently localized to cytokeratin-expressing epithelial cells. This study expands upon previous knowledge of FMDV pathogenesis in sheep by providing detailed information on the temporo-anatomic distribution of FMDV in ovine tissues. Findings are discussed in relation to similar investigations previously performed in cattle and pigs, highlighting similarities and differences in FMDV pathogenesis across natural host species.

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Section: Introductionmentioning

confidence: 99%

Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep

et al. 2019

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“…The same study also highlighted the likely importance of the oropharyngeal tonsils during early infection in swine (Stenfeldt et al, 2014b). A comparative assessment of simulated natural virus inoculations systems for sheep showed that both aerosol challenge and intranasopharyngeal deposition were valid alternatives to the conventional methods of coronary band inoculation and direct contact exposure (Stenfeldt et al, 2015). In cattle, experiments where FMDV-A24 was administered either into the tongue epithelium or by aerosol supported data from experiments using O serotype viruses, confirming that initial replication occurs in the nasopharynx, followed by expansion in the lung and systemic viraemia.…”

Section: Literature Reviewmentioning

confidence: 89%

“…The same study also highlighted the likely importance of the oropharyngeal tonsils during early infection in swine (Stenfeldt et al., ). A comparative assessment of simulated natural virus inoculations systems for sheep showed that both aerosol challenge and intranasopharyngeal deposition were valid alternatives to the conventional methods of coronary band inoculation and direct contact exposure (Stenfeldt et al., ).…”

Section: Pathogenesismentioning

confidence: 99%

“…Other studies of persistently infected cattle revealed that virus was most commonly associated with epithelial cells of the nasopharynx. In infected tissues, the levels of mRNA encoding several immuneoregulatory cytokines were reduced (Pacheco et al, 2015), raising interesting questions on the molecular interactions of FMDV with the host immune system. While unvaccinated cattle excrete significantly more virus and for longer, relative to vaccinated animals, a recent study casts doubt on the impact of vaccination on the frequency of development of carrier status (Parthiban et al, 2015a).…”

Section: Persistent Infectionmentioning

confidence: 99%

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Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology

Robinson

Knight-Jones

Charleston

et al. 2016

Transbound Emerg Dis

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SummaryWe assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain distribution. With ongoing advances, these areas could translate into significantly improved disease control.

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“…Pigs are more effectively infected through oral exposure, with primary infection occurring within epithelial crypts of the oropharyngeal-and laryngopharyngeal tonsils [32,47]. Fewer efforts have been invested into detailed study of the early stages of FMDV infection of small ruminants, but current evidence suggests that primary infection in sheep occurs in either epithelial crypts of the oropharyngeal-or laryngopharyngeal tonsils (similar to pigs), or within the nasopharyngeal mucosa (similar to cattle) [25,29].…”

Section: Temporo-anatomical Progression Of Fmdv Infectionmentioning

confidence: 99%

The Carrier Conundrum; A Review of Recent Advances and Persistent Gaps Regarding the Carrier State of Foot-and-Mouth Disease Virus

Stenfeldt

Arzt

2020

Pathogens

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The existence of a prolonged, subclinical phase of foot-and-mouth disease virus (FMDV) infection in cattle was first recognized in the 1950s. Since then, the FMDV carrier state has been a subject of controversy amongst scientists and policymakers. A fundamental conundrum remains in the discordance between the detection of infectious FMDV in carriers and the apparent lack of contagiousness to in-contact animals. Although substantial progress has been made in elucidating the causal mechanisms of persistent FMDV infection, there are still critical knowledge gaps that need to be addressed in order to elucidate, predict, prevent, and model the risks associated with the carrier state. This is further complicated by the occurrence of a distinct form of neoteric subclinical infection, which is indistinguishable from the carrier state in field scenarios, but may have substantially different epidemiological properties. This review summarizes the current state of knowledge of the FMDV carrier state and identifies specific areas of research in need of further attention. Findings from experimental investigations of FMDV pathogenesis are discussed in relation to experience gained from field studies of foot-and-mouth disease.

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Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems

Cited by 14 publications

References 32 publications

Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep

Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology

The Carrier Conundrum; A Review of Recent Advances and Persistent Gaps Regarding the Carrier State of Foot-and-Mouth Disease Virus

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