skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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

Abstract

The pathogenesis of foot-and-mouth disease virus (FMDV) in cattle was investigated through early and late stages of infection by use of an optimized experimental model for controlled contact exposure. Time-limited exposure of cattle to FMDV-infected pigs led to primary FMDV infection of the nasopharyngeal mucosa in both vaccinated and nonvaccinated cattle. In nonvaccinated cattle, the infection generalized rapidly to cause clinical disease, without apparent virus amplification in the lungs prior to establishment of viremia. Vaccinated cattle were protected against clinical disease and viremia; however, all vaccinated cattle were subclinically infected, and persistent infection occurred at similarly high prevalences in both animal cohorts. Infection dynamics in cattle were consistent and synchronous and comparable to those of simulated natural and needle inoculation systems. However, the current experimental model utilizes a natural route of virus exposure and is therefore superior for investigations of disease pathogenesis and host response. Deep sequencing of viruses obtained during early infection of pigs and cattle indicated that virus populations sampled from sites of primary infection were markedly more diverse than viruses from vesicular lesions of cattle, suggesting the occurrence of substantial bottlenecks associated with vesicle formation. These data expand previous knowledge of FMDV pathogenesis in cattle and providemore » novel insights for validation of inoculation models of bovine FMD studies. IMPORTANCE: Foot-and-mouth disease virus (FMDV) is an important livestock pathogen that is often described as the greatest constraint to global trade in animal products. The present study utilized a standardized pig-to-cow contact exposure model to demonstrate that FMDV infection of cattle initiates in the nasopharyngeal mucosa following natural virus exposure. Furthermore, this work confirmed the role of the bovine nasopharyngeal mucosa as the site of persistent FMDV infection in vaccinated and nonvaccinated cattle. The critical output of this study validates previous studies that have used simulated natural inoculation models to characterize FMDV pathogenesis in cattle and emphasizes the importance of continued research of the unique virus-host interactions that occur within the bovine nasopharynx. Specifically, vaccines and biotherapeutic countermeasures designed to prevent nasopharyngeal infection of vaccinated animals could contribute to substantially improved control of FMDV.« less

Authors:
ORCiD logo [1];  [2];  [2];  [3];  [4]; ORCiD logo [4];  [4];  [2]; ORCiD logo [2];  [5]
  1. US Dept. of Agriculture (USDA)-ARS, Freenport, NY (United States). Foreign Animal Disease Research Unit; Univ. of Minnesota, St. Paul, MN (United States). Dept of Veterinary Population Medicine
  2. US Dept. of Agriculture (USDA)-ARS, Freenport, NY (United States). Foreign Animal Disease Research Unit
  3. US Dept. of Agriculture (USDA)-ARS, Freenport, NY (United States). Foreign Animal Disease Research Unit; Kansas State Univ., Manhattan, KS (United States). Dept. of Diagnostic Medicine/Pathobiology
  4. US Dept. of Agriculture (USDA)-ARS, Freenport, NY (United States). Foreign Animal Disease Research Unit; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). PIADC Research Participation Program
  5. Univ. of Pittsburgh, PA (United States). School of Medicine
Publication Date:
Research Org.:
Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; USDA; US Department of Homeland Security (DHS)
OSTI Identifier:
1626159
Grant/Contract Number:  
SC0014664; 1940-32000-061-00D; HSHQDC-11-X-00131
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
mSphere
Additional Journal Information:
Journal Volume: 3; Journal Issue: 6; Journal ID: ISSN 2379-5042
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Microbiology; foot-and-mouth disease; foot-and-mouth disease virus; FMD; FMDV; cattle; pigs; virus; pathogenesis; NGS; transmission

Citation Formats

Stenfeldt, Carolina, Hartwig, Ethan J., Smoliga, George R., Palinski, Rachel, Silva, Ediane B., Bertram, Miranda R., Fish, Ian H., Pauszek, Steven J., Arzt, Jonathan, and Duprex, W. Paul. 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. United States: N. p., 2018. Web. doi:10.1128/msphere.00493-18.
Stenfeldt, Carolina, Hartwig, Ethan J., Smoliga, George R., Palinski, Rachel, Silva, Ediane B., Bertram, Miranda R., Fish, Ian H., Pauszek, Steven J., Arzt, Jonathan, & Duprex, W. Paul. 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. United States. https://doi.org/10.1128/msphere.00493-18
Stenfeldt, Carolina, Hartwig, Ethan J., Smoliga, George R., Palinski, Rachel, Silva, Ediane B., Bertram, Miranda R., Fish, Ian H., Pauszek, Steven J., Arzt, Jonathan, and Duprex, W. Paul. Wed . "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". United States. https://doi.org/10.1128/msphere.00493-18. https://www.osti.gov/servlets/purl/1626159.
@article{osti_1626159,
title = {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},
author = {Stenfeldt, Carolina and Hartwig, Ethan J. and Smoliga, George R. and Palinski, Rachel and Silva, Ediane B. and Bertram, Miranda R. and Fish, Ian H. and Pauszek, Steven J. and Arzt, Jonathan and Duprex, W. Paul},
abstractNote = {The pathogenesis of foot-and-mouth disease virus (FMDV) in cattle was investigated through early and late stages of infection by use of an optimized experimental model for controlled contact exposure. Time-limited exposure of cattle to FMDV-infected pigs led to primary FMDV infection of the nasopharyngeal mucosa in both vaccinated and nonvaccinated cattle. In nonvaccinated cattle, the infection generalized rapidly to cause clinical disease, without apparent virus amplification in the lungs prior to establishment of viremia. Vaccinated cattle were protected against clinical disease and viremia; however, all vaccinated cattle were subclinically infected, and persistent infection occurred at similarly high prevalences in both animal cohorts. Infection dynamics in cattle were consistent and synchronous and comparable to those of simulated natural and needle inoculation systems. However, the current experimental model utilizes a natural route of virus exposure and is therefore superior for investigations of disease pathogenesis and host response. Deep sequencing of viruses obtained during early infection of pigs and cattle indicated that virus populations sampled from sites of primary infection were markedly more diverse than viruses from vesicular lesions of cattle, suggesting the occurrence of substantial bottlenecks associated with vesicle formation. These data expand previous knowledge of FMDV pathogenesis in cattle and provide novel insights for validation of inoculation models of bovine FMD studies. IMPORTANCE: Foot-and-mouth disease virus (FMDV) is an important livestock pathogen that is often described as the greatest constraint to global trade in animal products. The present study utilized a standardized pig-to-cow contact exposure model to demonstrate that FMDV infection of cattle initiates in the nasopharyngeal mucosa following natural virus exposure. Furthermore, this work confirmed the role of the bovine nasopharyngeal mucosa as the site of persistent FMDV infection in vaccinated and nonvaccinated cattle. The critical output of this study validates previous studies that have used simulated natural inoculation models to characterize FMDV pathogenesis in cattle and emphasizes the importance of continued research of the unique virus-host interactions that occur within the bovine nasopharynx. Specifically, vaccines and biotherapeutic countermeasures designed to prevent nasopharyngeal infection of vaccinated animals could contribute to substantially improved control of FMDV.},
doi = {10.1128/msphere.00493-18},
url = {https://www.osti.gov/biblio/1626159}, journal = {mSphere},
issn = {2379-5042},
number = 6,
volume = 3,
place = {United States},
year = {2018},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share:

Works referenced in this record:

Foot-and-Mouth Disease
journal, April 2004


The economic impacts of foot and mouth disease – What are they, how big are they and where do they occur?
journal, November 2013


The Pathogenesis of Foot-and-Mouth Disease I: Viral Pathways in Cattle: Foot-and-Mouth Disease Pathogenesis in Cattle
journal, March 2011


The Pathogenesis and Diagnosis of Foot-and-Mouth Disease
journal, July 2003


The pathogenesis of natural and simulated natural foot-and-mouth disease infection in cattle
journal, October 1981


Pathogenesis of Primary Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Vaccinated and Non-Vaccinated Cattle
journal, November 2015


The Foot-and-Mouth Disease Carrier State Divergence in Cattle
journal, May 2016


Pathogenesis of foot-and-mouth disease: the lung as an additional portal of entry of the virus
journal, October 1976


Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle
journal, May 2017


Early events in the pathogenesis of foot-and-mouth disease in cattle after controlled aerosol exposure
journal, January 2010


Infection Dynamics of Foot-and-Mouth Disease Virus in Cattle Following Intranasopharyngeal Inoculation or Contact Exposure
journal, November 2016


Optimization of Immunohistochemical and Fluorescent Antibody Techniques for Localization of Foot-and-Mouth Disease Virus in Animal Tissues
journal, November 2009


Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses
journal, December 2017


Accumulation of nucleotide substitutions occurring during experimental transmission of foot-and-mouth disease virus
journal, October 2012


Evolution of foot-and-mouth disease virus intra-sample sequence diversity during serial transmission in bovine hosts
journal, January 2013


Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle
journal, October 2017


Evaluation of infectivity and transmission of different Asian foot-and-mouth disease viruses in swine
journal, January 2010


Transmission of Foot-and-Mouth Disease Virus during the Incubation Period in Pigs
journal, November 2016


Foot-and mouth diseases carriers
journal, August 1965


Improved techniques for the detection of foot-and-mouth disease virus in carrier cattle
journal, June 1967


Use of a portable real-time reverse transcriptasepolymerase chain reaction assay for rapid detection of foot-and-mouth disease virus
journal, June 2002


Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus.
journal, January 1989


MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004


MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets
journal, March 2016


    Works referencing / citing this record:

    Estimating viral bottleneck sizes for FMDV transmission within and between hosts and implications for the rate of viral evolution
    journal, December 2019


    Potential role of wildlife in the USA in the event of a foot-and-mouth disease virus incursion
    journal, April 2019


    The evolution of a super-swarm of foot-and-mouth disease virus in cattle
    journal, April 2019


    Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep
    journal, December 2019