title: Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus.
abstract: Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.
authors.affiliation: Animal Reproduction and Biotechnology Laboratory,Department of Biomedical Sciences,College of Veterinary Medicine and Biomedical Sciences,Colorado State University,CO 80523-1683,USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hansen
authors.affiliation: Animal Reproduction and Biotechnology Laboratory,Department of Biomedical Sciences,College of Veterinary Medicine and Biomedical Sciences,Colorado State University,CO 80523-1683,USA.
authors.forename: Natalia P
authors.initials: NP
authors.lastname: Smirnova
authors.affiliation: Veterinary Diagnostic Laboratory,North Dakota State University,ND,58108,USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Webb
authors.affiliation: Australian Infectious Diseases Research Centre & School of Veterinary Science University of Queensland,Queensland,Australia.
authors.forename: Helle
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.affiliation: Ruminant Diseases and Immunology Unit,National Animal Disease Center,USDA/ARS,IA 50010,USA.
authors.forename: Randy E
authors.initials: RE
authors.lastname: Sacco
authors.affiliation: Department of Microbiology,Immunology and Pathology,College of Veterinary Medicine and Biomedical Sciences,Colorado State University,CO 80523-1683,USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Van Campen
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology*; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D007113:Immunity, Innate / Q000502:physiology*; D007372:Interferons / Q000276:immunology; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000662:veterinary* / Q000821:virology
chemical_list: D007372:Interferons
keywords: IFN; adaptive; bovine viral diarrhea virus; fetus; immune response; innate; interferon; persistent infection