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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 pre-determined 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.

SUBMITTER: Stenfeldt C

PROVIDER: S-EPMC6938329 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Stenfeldt Carolina C Pacheco Juan M JM Singanallur Nagendrakumar B NB Vosloo Wilna W Rodriguez Luis L LL Arzt Jonathan J

PloS one 20191231 12

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-mort ...[more]

PMID: 31891626

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Project description:Under different circumstances, the alteration of several viral genes may give an evolutionary advantage to the virus to maintain its prevalence in nature. In this study, a 70-nucleotide deletion in the small fragment (S fragment) of the viral 5'-untranslated region (5'-UTR) together with one amino acid insertion in the leader protein (Lpro) that naturally occurred in several serotype O foot-and-mouth disease virus (FMDV) strains in China was identified. The properties of two field serotype O FMDV strains, with or without the 70-nucleotide deletion in the S fragment and the amino acid insertion in Lpro, were compared in vitro and in vivo Clinical manifestations of FMD were clearly observed in cattle and pigs infected by the virus without the mutations. However, the virus with the mentioned mutations caused FMD outcomes only in pigs, not in cattle. To determine the role of the 70-nucleotide deletion in the S fragment and the single amino acid insertion in Lpro in the pathogenicity and host range of FMDV, four recombinant viruses, with complete genomes and a 70-nucleotide deletion in the S fragment, a single amino acid insertion in Lpro, or both mutations, were constructed and rescued. It showed that deletion of 70 nucleotides in the S fragment or insertion of one amino acid (leucine) at position 10 of Lpro partly decreased the viral pathogenicity of Mya-98 lineage virus in cattle and pigs. However, the virus with dual mutations caused clinical disease only in pigs, not in cattle. This suggested that the S fragment and Lpro are significantly associated with the virulence and host specificity of FMDV. The naturally occurring dual mutation in the S fragment and Lpro is a novel determinant of viral pathogenicity and host range for serotype O FMDV.IMPORTANCE FMD is probably the most important livestock disease in the world due to the severe economic consequences caused. The alteration of several viral genes may give the virus selective advantage to maintain its prevalence in nature. Here, we identified that a 70-nucleotide deletion in the S fragment combined with a single leucine insertion in the leader protein (Lpro) is a novel determinant of restricted growth on bovine cells, which significantly contributes to the altered virulence of serotype O FMDV in cattle. A synergistic and additive effect of the 70-nucleotide deletion in the S fragment and the single leucine insertion in Lpro on the virulence and host specificity of the virus was determined. These results will benefit efforts to understand the vial pathogenicity mechanism and molecular characteristics of FMDV.

Dataset Information

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

Publications

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

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