Inhibition of Beta Interferon Transcription by Noncytopathogenic Bovine Viral Diarrhea Virus Is through an Interferon Regulatory Factor 3-Dependent Mechanism
| Autor: | Helen Flick-Smith, Stephen Goodbourn, M. D. Fray, Susan J. Baigent, Gang Zhang, John W. McCauley |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Myxovirus Resistance Proteins
Transcription Genetic animal diseases viruses Immunology Heterologous Apoptosis Semliki Forest virus Microbiology Virus Cytopathogenic Effect Viral GTP-Binding Proteins Interferon Virology medicine Animals Transcription factor Cells Cultured RNA Double-Stranded Diarrhea Viruses Bovine Viral biology Pestivirus Proteins virus diseases Interferon-beta biochemical phenomena metabolism and nutrition biology.organism_classification Semliki forest virus Virus-Cell Interactions DNA-Binding Proteins Insect Science Cattle Interferon Regulatory Factor-3 Tumor necrosis factor alpha Transcription Factors medicine.drug Interferon regulatory factors |
| Zdroj: | Journal of Virology. 76:8979-8988 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.76.18.8979-8988.2002 |
| Popis: | The induction and inhibition of the interferon (IFN) response and apoptosis by bovine viral diarrhea virus (BVDV) has been examined. Here we show that prior infection of cells by noncytopathogenic BVDV (ncp BVDV) fails to block transcriptional responses to alpha/beta IFN. In contrast, ncp BVDV-infected cells fail to produce IFN-α/β or MxA in response to double-stranded RNA (dsRNA) or infection with a heterologous virus (Semliki Forest virus [SFV]). ncp BVDV preinfection is unable to block cp BVDV- or SFV-induced apoptosis. The effects of ncp BVDV infection on the transcription factors controlling the IFN-β induction pathway have been analyzed. The transcription factor NF-κB was not activated following ncp BVDV infection, but ncp BVDV infection was not able to block the activation of NF-κB by either SFV or tumor necrosis factor alpha. Furthermore, ncp BVDV infection did not result in the activation of stress kinases (JNK1 and JNK2) or the phosphorylation of transcription factors ATF-2 and c-Jun; again, ncp BVDV infection was not able to block their activation by SFV. Interferon regulatory factor 3 (IRF-3) was shown to be translocated to the nuclei of infected cells in response to ncp BVDV, although DNA-binding of IRF-3 was not seen in nuclear extracts. In contrast, an IRF-3-DNA complex was observed in nuclear extracts from cells infected with SFV, but the appearance of this complex was blocked when cells were previously exposed to ncp BVDV. We conclude that the inhibition of IFN induction by this pestivirus involves a block to IRF-3 function, and we speculate that this may be a key characteristic for the survival of pestiviruses in nature. |
| Databáze: | OpenAIRE |
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