title: Infection of cultured bovine cells with bovine herpesvirus 1 (BHV-1) or Sendai virus induces different beta interferon subtypes.
abstract: In contrast to mice or humans, cattle contain three beta interferon (IFN-β) genes with distinct transcriptional promoters suggesting IFN-β gene expression is not stimulated the same by different viruses. To test this hypothesis, we compared expression of the three IFN-β subtypes after infection with a RNA virus, Sendai, versus a large DNA virus, bovine herpesvirus 1 (BHV-1). Infection of low passage bovine kidney (BK) or established bovine kidney cells (CRIB) with Sendai virus has consistently led to high levels of IFN-β1 RNA. Conversely, infection of CRIB cells, but not BK cells, with BHV-1 increased IFN-β3 RNA levels and to a lesser extent the other two IFN-β subtypes. Inhibition of de novo protein synthesis with cycloheximide resulted in higher levels of IFN-β1 and IFN-β2 RNA levels after BHV-1 infection. Further studies demonstrated that BHV-1 immediate early and/or early genes were primarily responsible for inhibiting the IFN response in BK cells. The three bovine IFN-β promoters were cloned upstream of a reporter gene construct, and their properties analyzed in transient transfection assays. Only the IFN-β3 promoter was trans-activated by IRF3 (interferon responsive factor 3). IRF7 and double stranded RNA (polyI:C) stimulated IFN-β1 and IFN-β3 promoter activity, but not IFN-β2. Relative to the human IFN-β promoter, the IFN-β3 promoter contained fewer nucleotide differences in the positive regulatory domain III (PRD III), PRD IV, and PRD I compared to the IFN-β1 and IFN-β2 promoter. Collectively, these studies provide evidence that virus infection differentially stimulates expression of the three bovine IFN-β genes.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, Fair Street at East Campus Loop, Lincoln, NE 68583-0905, USA.
authors.forename: Leticia Frizzo
authors.initials: LF
authors.lastname: da Silva
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques; D002460:Cell Line; D003001:Cloning, Molecular; D005809:Genes, Regulator; D017930:Genes, Reporter; D007242:Herpesvirus 1, Bovine / Q000378:metabolism*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis; D029082:Sendai virus / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D015534:Trans-Activators; D012313:RNA; D016899:Interferon-beta