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.
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.
School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, RM 234, Morisson Life Science Center, University of Nebraska, Lincoln, NE 68583, United States.
Leticia Frizzo
LF
da Silva
Devis
D
Sinani
Clinton
C
Jones
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic
D017874:Immediate-Early Proteins; D050505:Mutant Proteins; D016899:Interferon-beta