|Pacheco Tobin, Juan|
|O'DONNELL, VIVIAN - University Of Connecticut|
|BRITO-RODRIGUEZ, BARBARA - University Of California|
|STENFELDT, CAROLINA - Oak Ridge Institute For Science And Education (ORISE)|
Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/21/2015
Publication Date: 5/21/2015
Citation: Pacheco Tobin, J., Smoliga, G.R., O'Donnell, V., Brito-Rodriguez, B., Stenfeldt, C., Rodriguez, L.L., Arzt, J. 2015. Persistent foot-and-mouth disease virus infection in the nasopharynx of cattle: tissue-specific distribution and local cytokine expression. Virology. DOI:10.1371/journal.pone.0125698.
Interpretive Summary: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cattle, pigs, sheep, goats, and wild cloven-hoofed animals. The disease is characterized by fever and lesions of the mouth, tongue, feet, and teats. After infection of cattle, the FMD virus (FMDV) persists with no outward symptoms in 50 percent of affected animals for several months or years. This persistence, or “carrier”, stage of the disease is a potential threat for FMD-free countries, and has important economic impacts on international trade. The current study investigated tissue-specific localization of FMDV in persistently infected cattle to provide a detailed anatomic map of the distribution of FMDV infected tissues. In addition, immune responses are reported for these same tissues to suggest potential mechanisms for viral persistence. The overall conclusions were that specific tissues in the throat (nasopharynx surface) were the most frequent sites of FMDV infection and a trend of suppression in the production of proteins that regulate the immune process (cytokine expression) was identified.
Technical Abstract: Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall viral detection in the dorsal nasopharynx (80.95 percent) and dorsal soft palate (71.43 percent). FMDV was less frequently detected in laryngeal mucosal tissues, oropharyngeal mucosal sites, and lymph nodes draining the pharynx. Immunomicroscopy indicated that within persistently infected mucosal tissues, FMDV antigens were rarely detectable within epithelial cells in regions of mucosa-associated lymphoid tissue (MALT). Transcriptome analysis of persistently infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general trend of decreased mRNA levels compared to uninfected control animals. Although, statistically significant differences were not observed, greatest suppression of relative expression (RE) was identified for IP-10 (RE=0.198), IFN-B (RE=0.269), IL-12 (RE=0.275), and IL-2 (RE=0.312). Increased relative expression was detected for IL-6 (RE=2.065). Overall, this data demonstrates that during the FMDV carrier state in cattle, viral persistence is associated with epithelial cells of the nasopharynx in the upper respiratory tract and decreased presence of mRNA for several immunoregulatory cytokines in the infected tissues.