title: Foot-and-mouth disease virus virulence in cattle is co-determined by viral replication dynamics and route of infection.
abstract: Early events in the pathogenesis of foot-and-mouth disease virus (FMDV) infection in cattle were investigated through aerosol and intraepithelial lingual (IEL) inoculations of a cDNA-derived FMDV-A24 wild type virus (FMDV-WT) or a mutant derived from the same clone (FMDV-Mut). After aerosolization of FMDV-WT, primary infection sites had significantly greater quantities of FMDV, viral RNA, and type I/III interferon (IFN) activity compared to corresponding tissues from cattle infected with FMDV-Mut. Additionally, FMDV-WT-infected cattle had marked induction of systemic IFN activity in serum. In contrast, FMDV-Mut aerosol-infected cattle did not manifest systemic IFN response nor had viremia. Interestingly, IEL inoculation of FMDV-Mut in cattle restored the virulent phenotype and systemic IFN response. These data indicate that the attenuated phenotype in cattle is associated with decreased replicative efficiency, reflected by decreased innate response. However, attenuation is abrogated by bypassing the common primary infection sites, inducing accelerated viral replication at the inoculation site.
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Arzt
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pacheco
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Smoliga
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Meghan T
authors.initials: MT
authors.lastname: Tucker
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bishop
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Pauszek
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Ethan J
authors.initials: EJ
authors.lastname: Hartwig
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: de los Santos
authors.affiliation: From the Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island, NY, USA. Electronic address: luis.rodriguez@ars.usda.gov.
authors.forename: Luis L
authors.initials: LL
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology*; D005536:Foot-and-Mouth Disease / Q000235:genetics / Q000276:immunology / Q000821:virology*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D007113:Immunity, Innate; D007372:Interferons / Q000235:genetics / Q000276:immunology; D014774:Virulence; D014779:Virus Replication
chemical_list: D007372:Interferons
keywords: Attenuation; Bovine; Cattle; FMD; FMDV; Foot-and-mouth; Interferon; Pathogenesis; Virulence; Virus