title: Transplacental infection with non-cytopathic bovine viral diarrhoea virus types 1b and 2: viral spread and molecular neuropathology.
abstract: Infection with bovine viral diarrhoea virus (BVDV) represents a reproducible natural animal model in which to study mechanisms of transplacental viral infection. In the present study, BVDV-seronegative heifers were challenged intranasally with non-cytopathic BVDV of genotype 1b or 2. Fetuses were retrieved by caesarean section 7-114 days post-challenge of the dam and subjected to virological, histopathological and immunohistochemistry(IHC) studies. Gross and histopathological changes were only seen in fetuses infected at gestational age 75-85 days and retrieved at gestational age 190 days. Viral antigen could be detected in most tissues from 14 days post-infection, but the primary target organs for histopathological changes were brain, liver and spleen. In the brain, microscopical changes included leucomalacia and macrophage infiltration of meninges and neuropil. Viral antigen was detected in neurons, oligodendrocyte precursors and infiltrating macrophages. IHC revealed normal to slightly increased expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in the infected fetuses, with evidence of neuronal apoptosis and induction of inducible nitric oxide synthase (iNOS) and phospho-p38alpha mitogen-activated protein kinase (MAPK). These findings suggest that hypoxia may play only a limited role in the pathogenesis of the neural lesions. By contrast, virus-induced cytokine cascades, as part of the fetal innate immune response, and apoptosis of neurons and glial precursor cells may be central to the development of lesions.
authors.affiliation: Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. helle.ohmann@colostate.edu
authors.forename: H
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.forename: A-E
authors.initials: AE
authors.lastname: Tolnay
authors.forename: C E
authors.initials: CE
authors.lastname: Reisenhauer
authors.forename: T R
authors.initials: TR
authors.lastname: Hansen
authors.forename: N
authors.initials: N
authors.lastname: Smirnova
authors.forename: H
authors.initials: H
authors.lastname: Van Campen
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000473:pathology* / Q000821:virology; D001921:Brain / Q000196:embryology / Q000473:pathology / Q000821:virology; D002417:Cattle; D002418:Cattle Diseases / Q000473:pathology* / Q000821:virology; D002478:Cells, Cultured; D030241:Diarrhea Virus 1, Bovine Viral / Q000472:pathogenicity* / Q000502:physiology; D030242:Diarrhea Virus 2, Bovine Viral / Q000472:pathogenicity* / Q000502:physiology; D005260:Female; D005315:Fetal Diseases / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D005865:Gestational Age; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000821:virology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052248:Nitric Oxide Synthase Type I; D048051:p38 Mitogen-Activated Protein Kinases