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Title: Early Events in the Pathogenesis of Foot-and-Mouth Disease in Pigs; Identification of Oropharyngeal Tonsils as Sites of Primary and Sustained Viral Replication

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [2]
  1. US Department of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
  2. US Department of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center
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A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV) infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi) characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18–24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not colocalize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC); US Department of Homeland Security (DHS); National Pork Board
Grant/Contract Number:
SC0014664; HSHQDC-11-X-00189
OSTI ID:
1904891
Journal Information:
PLoS ONE, Vol. 9, Issue 9; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (12)

Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus journal February 2019
Contact Challenge of Cattle with Foot-and-Mouth Disease Virus Validates the Role of the Nasopharyngeal Epithelium as the Site of Primary and Persistent Infection journal December 2018
Early pathogenesis of the foot-and-mouth disease virus O/JPN/2010 in experimentally infected pigs journal January 2018
Pathogenesis of the attenuated foot-and-mouth disease virus O/JPN/2000 in experimentally infected pigs journal January 2018
Virus Excretion from Foot-And-Mouth Disease Virus Carrier Cattle and Their Potential Role in Causing New Outbreaks journal June 2015
Pathogenesis of Primary Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Vaccinated and Non-Vaccinated Cattle journal November 2015
Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep journal December 2019
The Different Tactics of Foot-and-Mouth Disease Virus to Evade Innate Immunity journal November 2018
The Pathogenesis of Foot-and-Mouth Disease in Pigs journal May 2016
Parameter Values for Epidemiological Models of Foot-and-Mouth Disease in Swine journal June 2016
Transmission of Foot-and-Mouth Disease Virus during the Incubation Period in Pigs journal November 2016
Foot-and-Mouth Disease Infection Dynamics in Contact-Exposed Pigs Are Determined by the Estimated Exposure Dose journal July 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
swine
tonsils
palate
epithelium
euthanasia
foot and mouth disease
epithelial cells
lesions