ICP27 protein encoded by bovine herpesvirus type 1 (bICP27) interferes with promoter activity of the bovine genes encoding beta interferon 1 (IFN-β1) and IFN-β3

Abstract

Bovine herpes virus 1 (BHV-1) infection leads to upper respiratory tract infections, conjunctivitis, and the infection predisposes cattle to secondary bacterial infections. The infected cell protein 0 (bICP0) encoded by BHV-1 suppresses antiviral innate immune signaling by interfering with expression of interferon beta (IFN-β). In contrast to humans or mice, cattle contain three IFN-β genes that have distinct transcriptional promoters. We previously cloned and characterized all three bovine IFN-β promoters. In this study, we provide evidence that bICP27; a viral early protein that shuttles between the nucleus and cytoplasm inhibits transcriptional activity of two bovine IFN-β gene promoters (IFN-β1 and IFN-β3). Conversely, the BHV-1 infected cell protein 0 (bICP0) early promoter was not inhibited by bICP27. C-terminal mutants lacking the bICP27 zinc RING finger-like motif did not efficiently inhibit IFN-β3 promoter activity but inhibited IFN-β1 promoter activity as efficiently as wild type bICP27. An N-terminal mutant lacking the nuclear localization signal (NLS) and nucleolar localization signal (NoLS) was localized to the cytoplasm and this mutant had no effect on IFN-β promoter activity. In summary, these studies provided evidence that bICP27 inhibited IFN-β1 and IFN-β3 promoter activity in transiently transfected cells.