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

Abstract

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.

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

“…Similar findings were subsequently confirmed, indicating that high proportions of both sheep and goats became FMDV carriers after contact exposure or intranasal instillation and that nearly 50% of sheep remained as carriers 9 months after infection [77]. A recent publication confirmed the localization of persistent FMDV to epithelial crypts within ovine oropharyngeal and laryngopharyngeal tonsils [29]. This finding was similar across naïve and vaccinated cohorts of sheep.…”

“…This finding was similar across naïve and vaccinated cohorts of sheep. However, the administration of a high payload vaccine (> 6 PD 50 ) 14 days prior to virus challenge prevented FMDV persistence, even though all animals were confirmed to have been infected after challenge [29,78]. The combined output of FMDV pathogenesis studies in sheep thus suggest that although virus detection during early infection shares similarities with both cattle and pigs, the anatomic localization of persistent FMDV may be more similar to infection in African buffalo.…”

“…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].…”

Airborne Transmission of Foot-and-Mouth Disease Virus: A Review of Past and Present Perspectives

“…Studies which aim to measure the efficiency of aerosols as a route of infection also describe an experimental set up designed to mimic a natural route of infection ( Figure 2 ). These studies have shown infectious FMDV and FMDV RNA was detected from the oral cavities of cattle [ 26 ] and sheep [ 27 , 28 ] after they were challenged using nebulised virus and a fitted face mask, with delivery of virus aerosols into the nostrils of recipient animals. Additionally, between-pen transmission experiments have been performed whereby needle-inoculated donor animals are placed in one room and contact animals in adjoining pens with a free flow of air between the pens.…”

Viral Population Diversity during Co-Infection of Foot-And-Mouth Disease Virus Serotypes SAT1 and SAT2 in African Buffalo in Kenya

“…In domestic livestock, FMD is characterized by an acute clinical phase of infection consisting of fever and vesicles that resolve within two weeks. However, FMDV also causes long-term subclinical, persistent infection in epithelial cells of the nasopharynx of cattle [ 8 , 9 ] and oropharyngeal tonsils of sheep [ 10 , 11 ]. Additionally, there is an early form of subclinical infection (neoteric phase) which has higher levels of shedding and transmissibility compared to the persistent phase [ 9 ].…”