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:

Stenfeldt, Carolina  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-2074-3886"

Hartwig, Ethan J. ^[2]; Smoliga, George R. ^[2]; Palinski, Rachel ^[3]; Silva, Ediane B. ^[4]; Bertram, Miranda R.  ^[4];

• Search DOE PAGES for author "Bertram, Miranda R."
• Search DOE PAGES for ORCID "0000-0003-3321-960X"

Fish, Ian H. ^[4]; Pauszek, Steven J. ^[2]; Arzt, Jonathan  ^[2];

• Search DOE PAGES for author "Arzt, Jonathan"
• Search DOE PAGES for ORCID "0000-0002-7517-7893"

Duprex, W. Paul ^[5]

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+ Show Author Affiliations

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:

Wed Dec 12 00:00:00 EST 2018

Research Org.:

Oak Ridge Institute 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:

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