title: A bovine respiratory syncytial virus model with high clinical expression in calves with specific passive immunity.
abstract: BACKGROUND
  Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide. Calves are particularly affected, even with low to moderate levels of BRSV-specific maternally derived antibodies (MDA). Available BRSV vaccines have suboptimal efficacy in calves with MDA, and published infection models in this target group are lacking in clinical expression. Here, we refine and characterize such a model.
  
  
  RESULTS
  In a first experiment, 2 groups of 3 calves with low levels of MDA were experimentally inoculated by inhalation of aerosolized BRSV, either: the Snook strain, passaged in gnotobiotic calves (BRSV-Snk), or isolate no. 9402022 Denmark, passaged in cell culture (BRSV-Dk). All calves developed clinical signs of respiratory disease and shed high titers of virus, but BRSV-Snk induced more severe disease, which was then reproduced in a second experiment in 5 calves with moderate levels of MDA. These 5 calves shed high titers of virus and developed severe clinical signs of disease and extensive macroscopic lung lesions (mean+/-SD, 48.3+/-12.0% of lung), with a pulmonary influx of inflammatory cells, characterized by interferon gamma secretion and a marked effect on lung function.
  
  
  CONCLUSIONS
  We present a BRSV-infection model, with consistently high clinical expression in young calves with low to moderate levels of BRSV-specific MDA, that may prove useful in studies into disease pathogenesis, or evaluations of vaccines and antivirals. Additionally, refined tools to assess the outcome of BRSV infection are described, including passive measurement of lung function and a refined system to score clinical signs of disease. Using this cognate host calf model might also provide answers to elusive questions about human RSV (HRSV), a major cause of morbidity in children worldwide.
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Uppsala, Sweden. krister.blodorn@slu.se.
authors.forename: Krister
authors.initials: K
authors.lastname: Blodörn
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Uppsala, Sweden. sara.hagglund@slu.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Hägglund
authors.affiliation: Department of Pathology and Wildlife Diseases, National Veterinary Institute, Uppsala, Sweden. dolores.gavier-widen@sva.se.|Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. dolores.gavier-widen@sva.se.
authors.forename: Dolores
authors.initials: D
authors.lastname: Gavier-Widen
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France. jean-francois.eleouet@jouy.inra.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eléouët
authors.affiliation: INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France. sabine.riffault@jouy.inra.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Uppsala, Sweden. john.pringle@slu.se.
authors.forename: John
authors.initials: J
authors.lastname: Pringle
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, UK. geraldine.taylor@pirbright.ac.uk.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Taylor
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Uppsala, Sweden. jean-francois.valarcher@slu.se.|Department of Virology, National Veterinary Institute, Immunology, and Parasitology, Uppsala, Sweden. jean-francois.valarcher@slu.se.
authors.forename: Jean François
authors.initials: JF
authors.lastname: Valarcher
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology / Q000821:virology; D000914:Antibodies, Viral / Q000276:immunology; D002417:Cattle / Q000276:immunology / Q000821:virology; D002418:Cattle Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D007116:Immunization, Passive / Q000662:veterinary; D008168:Lung / Q000473:pathology; D008297:Male; D018448:Models, Immunological; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral