Progress 09/15/05 to 09/14/08
Outputs
OUTPUTS: Bovine herpes virus 1 (BHV-1) can cause clinical symptoms in cattle and induce "shipping fever," which costs the industry more than $3 billion per year. Current vaccines can be pathogenic to small calves, cause abortions, and do not prevent latency of wild-type virus. BHV-1 establishes latency, but can reactivate, in part, because the bICP0 protein activates viral gene expression. bICP0 can activate expression of all three classes of viral genes, is expressed throughout productive infection, and is thus considered to be the most important viral regulatory gene. We have demonstrated that a C3HC4 zinc ring finger near the amino terminus of bICP0 plays an important role in activating transcription and productive infection. In addition, bICP0 inhibits interferon (IFN) dependent transcription, in part, because it induces degradation of a critical transcriptional activator of the IFN-beta promoter. Furthermore, bICP0 interacts with chromatin remodeling enzymes {histone deacytlase 1 (HDAC1) and a histone acetylase (p300)}. We have recently developed mutant viruses containing mutations in the C3HC4 zinc ring finger. These mutant virus strains do not grow efficiently in calves or cultured cells, and are unable to reactivate from latency. These studies have demonstrated that bICP0 is crucial for productive infection and pathogenesis. We believe that regulating bICP0 functions may improve exisiting modified live vaccines. PARTICIPANTS: Although most of the work was performed by scientists at UNL, Dept of VBMS we do have an active collaboration with Dr. Shafiqul Chowdhury who has been at Kansas State University, College of Veterinary Medicine. Furthermore, we have a collaboration with Dr. Alan Doster in VDC at UNL. These collaborations have been significant interactions with experts in related fields. TARGET AUDIENCES: Scientists, ranchers, vaccine companies, and generally individuals who are interested in bovine disease. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
BHV-1 is an important pathogen of cattle, which costs the cattle industry $3 billion/year in the US. These studies will help us understand bICP0 function and its relationship to disease. The knowledge derived from these studies may help design novel strategies for designing modified live vaccines that induce immunity, do not cause disease in cattle, and do not reactivate from latency.
Publications
- Saira, K., S. Chowdhury, N. Gaudreault, L. da Silva, G. Henderson, A. Doster, and C. Jones. 2008. The zinc RING finger of the bovine herpesvirus 1 encoded bICP0 protein is crucial for viral replication and virulence. in press, J of Virology.
- Zhang, Y. and C. Jones. 2005. Identification of functional domains within the bICP0 protein encoded by bovine herpesvirus 1 (BHV-1). J Gen Virol 86:879-886.
- Geiser, V., Y. Zhang, & C. Jones. 2005. Analysis of a bovine herpesvirus 1 (BHV-1) recombinant virus that does not express the bICP0 protein. J Gen Virol 86:1987-1996.
- Henderson, G., Y. Zhang, and C. Jones. 2005. The bovine herpesvirus 1 (BHV-1) gene encoding infected cell protein 0 (bICP0) can inhibit interferon dependent transcription in the absence of other viral genes. J G Virology 86: 2697-2702.
- Saira, K. and C. Jones. 2007. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 (IRF3), and consequently inhibits beta interferon promoter activity. J Virology 81:3077-3086.
- Geiser, V., S. Rose, and C. Jones. 2008. Bovine herpesvirus type 1 induces cell death by a cell type dependent fashion. Microbial Pathogenesis 44:459-466.
- Jones, C. and S. Chowdhury. 2008. A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex, and development of improved vaccines. Adv in Animal Health, 8:187-205.
- Meyer, F. and C. Jones. 2008. C/EBP-alpha cooperates with bTIF to activate the bovine herpesvirus 1 immediate early transcription unit 1 promoter. IN PRESS, J. Neurovirology.
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Progress 09/15/06 to 09/14/07
Outputs
Bovine herpes virus 1 (BHV-1) can cause clinical symptoms in cattle and induce "shipping fever," which costs the industry more than $640 million per year. Current vaccines can be pathogenic to small calves, cause abortions, and do not prevent latency of wild-type virus. BHV-1 establishes latency but can reactivate, in part, because the bICP0 protein activates viral gene expression. bICP0 can activate expression of all three classes of viral genes, is expressed throughout productive infection, and is thus considered to be the most important viral regulatory gene. We have demonstrated that a C3HC4 zinc ring finger near the amino terminus of bICP0 plays an important role in activating transcription and productive infection. Furthermore, bICP0 interacts with two cellular transcription factors {histone deacytlase 1 (HDAC1) and a histone acetylase (p300)}. These interactions with host transcription factors stimulate viral transcription. We have also demonstrated that bICP0
inhibits innate immune responses, in part by inhibiting activation of interferon dependent transcription. The ability of bICP0 to induce degradation of interferon regulatory factor 3 (IRF3) is important in this process. These studies will help us understand bICP0 function and its relationship to disease and may help the vaccine industry design modified live vaccines that induce immunity, do not cause disease in cattle, and do not reactivate from latency.
Impacts
We hope to identify critical domains within bICP0 that can be mutated, in order to develop a better modified live vaccine.
Publications
- Zhang, Y., Y. Jiang, J. Zhou, V. Geiser, & C. Jones. 2006. The bovine herpes virus 1 (BHV-1) immediate early protein (bICP0) interacts with the histone acetyltransferase p300, and these interactions correlate with stimulation of gC promoter activity. J Gen Virol 87: 1843-1851.
- Perez, S., F. Meyer, G. Henderson, Y. Jiang, S. Sherman, A. Doster, M. Inman, and C. Jones. 2007. A protein encoded by the bovine herpesvirus 1 ORF E gene induces neurite-like morphological changes in mouse neuroblastoma cells and is expressed in trigeminal ganglionic neurons. J Neurovirol, IN PRESS.
- Saira, K. and C. Jones. 2007. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 (IRF3), and consequently inhibits beta interferon promoter activity. J Virol, IN PRESS.
- Jones, C., V. Geiser, G. Henderson, Y. Jiang, F. Meyer, S. Perez, Y. Zhang. 2006. Functional analysis of bovine herpesvirus 1 (BHV-1) genes expressed during latency. Vet Micro 113:199-210.
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Progress 09/15/05 to 09/15/06
Outputs
Bovine herpes virus 1 (BHV-1) can cause clinical symptoms in cattle and induce shipping fever, which costs the industry more than $640 million per year. Current vaccines can be pathogenic to small calves, cause abortions, and do not prevent latency of wild-type virus. BHV-1 establishes latency, but can reactivate, in part, because the bICP0 protein activates viral gene expression. bICP0 can activate expression of all three classes of viral genes, is expressed throughout productive infection, and is thus considered to be the most important viral regulatory gene. We have demonstrated that a C3HC4 zinc ring finger near the amino terminus of bICP0 plays an important role in activating transcription and productive infection. Furthermore, bICP0 interacts with chromatin remodeling enzymes {histone deacytlase 1 (HDAC1) and a histone acetylase (p300)}. Recent studies have demonstrated that bICP0 also inhibits interferon dependent transcription, suggesting that bICP0 regulates
innate immune responses. We have recently developed a mutant BHV-1 strain that does not grow efficiently. This mutant grows poorly and does not form well-defined plaques. The mutant virus establishes a persistent infection in cultured bovine cells. In summary, our studies suggest that bICP0 is crucial for productive infection.
Impacts
BHV-1 is an important pathogen of cattle, which costs the cattle industry one-half billion dollars per year in the US. These studies will help us understand bICP0 function and its relationship to disease and may help the vaccine industry design modified live vaccines that induce immunity, do not cause disease in cattle, and do not reactivate from latency.
Publications
- Henderson, G., Y. Zhang, and C. Jones. 2005. The bovine herpesvirus 1 (BHV-1) gene encoding infected cell protein 0 (bICP0) can inhibit interferon dependent transcription in the absence of other viral genes. J. of G. Virology, 86: 2697-2702
- Jones, C., V. Geiser, G. Henderson, Y. Jiang, F. Meyer, S. Perez, Y. Zhang. 2005. Functional analysis of bovine herpesvirus 1 (BHV-1) genes expressed during latency. Veterinary Microbiology, IN PRESS
- Zhang, Y., Y. Jiang, J. Zhou & C. Jones. 2005. The bovine herpes virus 1 (BHV-1) immediate early protein (bICP0) interacts with the histone acetyltransferase p300, and these interactions correlate with stimulation of gC promoter activity. Submitted to J. of General Virology
- Henderson, G., Y. Zhang, M. Inman, D. Jones and C. Jones. 2004. Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3 when overexpressed in transfected cells. J Gen Virol ; 85: 3511-3516
- Zhang, Y. and C. Jones. 2005. Identification of functional domains within the bICP0 protein encoded by bovine herpesvirus 1 (BHV-1). J. of General Virology, 86:879-886
- Geiser, V., Y. Zhang, & C. Jones. 2005. Analysis of a bovine herpesvirus 1 (BHV-1) recombinant virus that does not express the bICP0 protein. J. of General Virology. 86: 1987-1996
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