Title: Pathogenesis of Primary Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Vaccinated and Non-Vaccinated Cattle

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [2];  [3];  [3];  [4]
  1. US Dept. of Agriculture (USDA), Greenport, NY (United States). Plum Island Animal Disease Center; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States); OSTI
  2. US Dept. of Agriculture (USDA), Greenport, NY (United States). Plum Island Animal Disease Center; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
  3. US Dept. of Agriculture (USDA), Greenport, NY (United States). Plum Island Animal Disease Center
  4. Univ. of Georgia, Athens, GA (United States)

A time-course pathogenesis study was performed to compare and contrast primary footand-mouth disease virus (FMDV) infection following simulated-natural (intra-nasopharyngeal) virus exposure of cattle that were non-vaccinated or vaccinated using a recombinant adenovirus-vectored FMDV vaccine. FMDV genome and infectious virus were detected during the initial phase of infection in both categories of animals with consistent predilection for the nasopharyngeal mucosa. A rapid progression of infection with viremia and widespread dissemination of virus occurred in non-vaccinated animals whilst vaccinated cattle were protected from viremia and clinical FMD. Analysis of micro-anatomic distribution of virus during early infection by lasercapture microdissection localized FMDV RNA to follicleassociated epithelium of the nasopharyngeal mucosa in both groups of animals, with concurrent detection of viral genome in nasopharyngeal MALT follicles in vaccinated cattle only. FMDV structural and non-structural proteins were detected in epithelial cells of the nasopharyngeal mucosa by immunomicroscopy 24 hours after inoculation in both non-vaccinated and vaccinated steers. Co-localization of CD11c+ /MHC II+ cells with viral protein occurred early at primary infection sites in vaccinated steers while similar host-virus interactions were observed at later time points in non-vaccinated steers. Additionally, numerous CD8+ /CD3- host cells, representing presumptive natural killer cells, were observed in association with foci of primary FMDV infection in the nasopharyngeal mucosa of vaccinated steers but were absent in non-vaccinated steers. Immunomicroscopic evidence of an activated antiviral response at primary infection sites of vaccinated cattle was corroborated by a relative induction of interferon -α, -β, -γ and -λ mRNA in micro-dissected samples of nasopharyngeal mucosa. Although vaccination protected cattle from viremia and clinical FMD, there was subclinical infection of epithelial cells of the nasopharyngeal mucosa that could enable shedding and long-term persistence of infectious virus. Additionally, these data indicate different mechanisms within the immediate host response to infection between nonvaccinated and vaccinated cattle.

Research Organization:
Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
US Dept. of Homeland Security (DHS); USDOE Office of Science (SC)
Grant/Contract Number:
SC0014664
OSTI ID:
1904939
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 11 Vol. 10; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (78)

Plasmacytoid dendritic cell activation by foot-and-mouth disease virus requires immune complexes journal July 2006
Development of a novel quantitative real-time RT-PCR assay for the simultaneous detection of all serotypes of Foot-and-mouth disease virus journal October 2003
The pathogenesis of natural and simulated natural foot-and-mouth disease infection in cattle journal October 1981
A continuous bovine kidney cell line for routine assays of foot-and-mouth disease virus journal September 1988
Modulation of Cytokine mRNA Expression in Pharyngeal Epithelial Samples obtained from Cattle Infected with Foot-and-Mouth Disease Virus journal February 2012
Identification of a major antibody binding epitope in the non-structural protein 3D of foot-and-mouth disease virus in cattle and the development of a monoclonal antibody with diagnostic applications journal April 2007
Early events in the pathogenesis of foot-and-mouth disease in cattle after controlled aerosol exposure journal January 2010
Secretory IgA as an indicator of oro-pharyngeal foot-and-mouth disease virus replication and as a tool for post vaccination surveillance journal February 2006
Bovine natural killer cells journal August 2009
Detection of carriers of foot-and-mouth disease virus among vaccinated cattle journal November 2004
Detection of foot-and-mouth disease virus RNA in pharyngeal epithelium biopsy samples obtained from infected cattle: Investigation of possible sites of virus replication and persistence journal January 2012
Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems journal July 2015
Foot-and-mouth disease virus virulence in cattle is co-determined by viral replication dynamics and route of infection journal March 2014
Validation of an Mx/CAT reporter gene assay for the quantification of bovine type-I interferon journal March 2001
Experimental studies with foot-and-mouth disease virus, strain O, responsible for the 2001 epidemic in the United Kingdom journal June 2002
Observations on the carrier state and related antibody titres during an outbreak of foot-and-mouth disease journal March 1970
Studies on the carrier state of cattle exposed to foot-and-mouth disease virus journal March 1966
Growth of foot-and-mouth disease virus in the upper respiratory tract of non-immunized, vaccinated, and recovered cattle after intranasal inoculation journal June 1976
MALT structure and function in farm animals journal February 2006
The Localization of Persistent Foot and Mouth Disease Virus in the Epithelial Cells of the Soft Palate and Pharynx journal February 2001
The Pathogenesis of Foot-and-Mouth Disease I: Viral Pathways in Cattle: Foot-and-Mouth Disease Pathogenesis in Cattle journal March 2011
Factors Associated With Within-Herd Transmission of Serotype A Foot-and-Mouth Disease Virus in Cattle, During the 2001 Outbreak in Argentina: A Protective Effect of Vaccination: Within-Herd Transmission FMD journal March 2011
Foot-and-Mouth Disease journal April 2004
Bovine Type III Interferon Significantly Delays and Reduces the Severity of Foot-and-Mouth Disease in Cattle journal February 2012
Analysis of a Foot-and-Mouth Disease Virus Type A24 Isolate Containing an SGD Receptor Recognition Site In Vitro and Its Pathogenesis in Cattle journal September 2005
The Early Pathogenesis of Foot-and-Mouth Disease in Cattle After Aerosol Inoculation: Identification of the Nasopharynx as the Primary Site of Infection journal June 2010
Optimization of Immunohistochemical and Fluorescent Antibody Techniques for Localization of Foot-and-Mouth Disease Virus in Animal Tissues journal November 2009
Transcriptome and de novo analysis of Rosa xanthina f. spontanea in response to cold stress journal October 2021
Matrix-M™ Adjuvant Induces Local Recruitment, Activation and Maturation of Central Immune Cells in Absence of Antigen journal July 2012
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 September 2014
Use of a portable real-time reverse transcriptasepolymerase chain reaction assay for rapid detection of foot-and-mouth disease virus journal June 2002
Plasmacytoid dendritic cell activation by foot-and-mouth disease virus requires immune complexes journal July 2006
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method journal December 2001
Development of a novel quantitative real-time RT-PCR assay for the simultaneous detection of all serotypes of Foot-and-mouth disease virus journal October 2003
The pathogenesis of natural and simulated natural foot-and-mouth disease infection in cattle journal October 1981
Emergency vaccination against foot-and-mouth disease: Rate of development of immunity and its implications for the carrier state journal January 1994
A continuous bovine kidney cell line for routine assays of foot-and-mouth disease virus journal September 1988
The Pathogenesis and Diagnosis of Foot-and-Mouth Disease journal July 2003
Validation of an Mx/CAT reporter gene assay for the quantification of bovine type-I interferon journal March 2001
Experimental studies with foot-and-mouth disease virus, strain O, responsible for the 2001 epidemic in the United Kingdom journal June 2002
Aspects of the persistence of foot-and-mouth disease virus in animals—the carrier problem journal August 2002
Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination journal September 2014
Modulation of Cytokine mRNA Expression in Pharyngeal Epithelial Samples obtained from Cattle Infected with Foot-and-Mouth Disease Virus journal February 2012
Identification of a major antibody binding epitope in the non-structural protein 3D of foot-and-mouth disease virus in cattle and the development of a monoclonal antibody with diagnostic applications journal April 2007
Early events in the pathogenesis of foot-and-mouth disease in cattle after controlled aerosol exposure journal January 2010
Protection against direct-contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx journal January 2005
Secretory IgA as an indicator of oro-pharyngeal foot-and-mouth disease virus replication and as a tool for post vaccination surveillance journal February 2006
Effect of emergency FMD vaccine antigen payload on protection, sub-clinical infection and persistence following direct contact challenge of cattle journal April 2006
Innate immune responses against foot-and-mouth disease virus: Current understanding and future directions journal March 2009
Bovine natural killer cells journal August 2009
Detection of carriers of foot-and-mouth disease virus among vaccinated cattle journal November 2004
Detection of foot-and-mouth disease virus RNA in pharyngeal epithelium biopsy samples obtained from infected cattle: Investigation of possible sites of virus replication and persistence journal January 2012
Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems journal July 2015
Foot-and-mouth disease virus virulence in cattle is co-determined by viral replication dynamics and route of infection journal March 2014
Observations on the carrier state and related antibody titres during an outbreak of foot-and-mouth disease journal March 1970
Studies on the carrier state of cattle exposed to foot-and-mouth disease virus journal March 1966
Growth of foot-and-mouth disease virus in the upper respiratory tract of non-immunized, vaccinated, and recovered cattle after intranasal inoculation journal June 1976
Dexamethasone inhibits virus production and the secretory IgA response in oesophageal–pharyngeal fluid in cattle persistently infected with foot-and-mouth disease virus journal April 1997
MALT structure and function in farm animals journal February 2006
The Localization of Persistent Foot and Mouth Disease Virus in the Epithelial Cells of the Soft Palate and Pharynx journal February 2001
The Pathogenesis of Foot-and-Mouth Disease I: Viral Pathways in Cattle: Foot-and-Mouth Disease Pathogenesis in Cattle journal March 2011
Factors Associated With Within-Herd Transmission of Serotype A Foot-and-Mouth Disease Virus in Cattle, During the 2001 Outbreak in Argentina: A Protective Effect of Vaccination: Within-Herd Transmission FMD journal March 2011
Foot-and-Mouth Disease journal April 2004
A Continuous Bovine Kidney Cell Line Constitutively Expressing Bovine  V 6 Integrin Has Increased Susceptibility to Foot-and-Mouth Disease Virus journal March 2013
Bovine Type III Interferon Significantly Delays and Reduces the Severity of Foot-and-Mouth Disease in Cattle journal February 2012
Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus. journal January 1989
Analysis of a Foot-and-Mouth Disease Virus Type A24 Isolate Containing an SGD Receptor Recognition Site In Vitro and Its Pathogenesis in Cattle journal September 2005
The Early Pathogenesis of Foot-and-Mouth Disease in Cattle After Aerosol Inoculation: Identification of the Nasopharynx as the Primary Site of Infection journal June 2010
Optimization of Immunohistochemical and Fluorescent Antibody Techniques for Localization of Foot-and-Mouth Disease Virus in Animal Tissues journal November 2009
Analysis of the acute phase responses of Serum Amyloid A, Haptoglobin and Type 1 Interferon in cattle experimentally infected with foot-and-mouth disease virus serotype O journal January 2011
Foot-and-Mouth Disease Virus Persists in the Light Zone of Germinal Centres journal October 2008
Matrix-M™ Adjuvant Induces Local Recruitment, Activation and Maturation of Central Immune Cells in Absence of Antigen journal July 2012
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 September 2014
Phenotypic, Ultra-Structural, and Functional Characterization of Bovine Peripheral Blood Dendritic Cell Subsets journal October 2014
Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle; Tissue-Specific Distribution and Local Cytokine Expression journal May 2015
Virus Excretion from Foot-And-Mouth Disease Virus Carrier Cattle and Their Potential Role in Causing New Outbreaks journal June 2015
Adenovirus serotype 5-vectored foot-and-mouth disease subunit vaccines: the first decade journal January 2010
Use of a portable real-time reverse transcriptasepolymerase chain reaction assay for rapid detection of foot-and-mouth disease virus journal June 2002

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The Foot-and-Mouth Disease Carrier State Divergence in Cattle journal May 2016
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
Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine journal September 2016
Proof-of-concept study: profile of circulating microRNAs in Bovine serum harvested during acute and persistent FMDV infection journal April 2017
Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle journal May 2017
Early pathogenesis of the foot-and-mouth disease virus O/JPN/2010 in experimentally infected pigs journal January 2018
Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx journal September 2016
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
Foot-and-Mouth Disease Infection Dynamics in Contact-Exposed Pigs Are Determined by the Estimated Exposure Dose journal July 2018
Parameterization of the Durations of Phases of Foot-And-Mouth Disease in Cattle journal August 2019
Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease journal August 2020