Infection of cultured bovine cells with bovine herpesvirus 1 (BHV-1) or Sendai virus induces different beta interferon subtypes.

摘要

In contrast to mice or humans, cattle contain three beta interferon (IFN-beta) genes with distinct transcriptional promoters suggesting IFN-beta gene expression is not stimulated the same by different viruses. To test this hypothesis, we compared expression of the three IFN-beta 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-beta1 RNA. Conversely, infection of CRIB cells, but not BK cells, with BHV-1 increased IFN-beta3 RNA levels and to a lesser extent the other two IFN-beta subtypes. Inhibition of de novo protein synthesis with cycloheximide resulted in higher levels of IFN-beta1 and IFN-beta2 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-beta promoters were cloned upstream of a reporter gene construct, and their properties analyzed in transient transfection assays. Only the IFN-beta3 promoter was trans-activated by IRF3 (interferon responsive factor 3). IRF7 and double stranded RNA (polyI:C) stimulated IFN-beta1 and IFN-beta3 promoter activity, but not IFN-beta2. Relative to the human IFN-beta promoter, the IFN-beta3 promoter contained fewer nucleotide differences in the positive regulatory domain III (PRD III), PRD IV, and PRD I compared to the IFN-beta1 and IFN-beta2 promoter. Collectively, these studies provide evidence that virus infection differentially stimulates expression of the three bovine IFN-beta genes.