scholarly journals The NPro Product of Bovine Viral Diarrhea Virus Inhibits DNA Binding by Interferon Regulatory Factor 3 and Targets It for Proteasomal Degradation

2006 ◽  
Vol 80 (23) ◽  
pp. 11723-11732 ◽  
Author(s):  
Louise Hilton ◽  
Kartykayan Moganeradj ◽  
Gang Zhang ◽  
Yun-Hsiang Chen ◽  
Richard E. Randall ◽  
...  
Keyword(s):  
Bovine Viral Diarrhea Virus ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Bovine Viral Diarrhea ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

ABSTRACT Bovine viral diarrhea virus (BVDV) is a pestivirus that can establish a persistent infection in the developing fetus and has the ability to disable the production of type I interferon. In this report, we extend our previous observations that BVDV encodes a protein able to specifically block the activity of interferon regulatory factor 3 (IRF-3), a transcription factor essential for interferon promoter activation, by demonstrating that this is a property of the N-terminal protease fragment (NPro) of the BVDV polyprotein. Although BVDV infections cause relocalization of cellular IRF-3 from the cytoplasm to the nucleus early in infection, NPro blocks IRF-3 from binding to DNA. NPro has the additional property of targeting IRF-3 for polyubiquitination and subsequent destruction by cellular multicatalytic proteasomes. The autoprotease activity of NPro is not required for the inhibition of type I interferon induction or the targeting of IRF-3 for degradation.

scholarly journals Inhibition of Beta Interferon Transcription by Noncytopathogenic Bovine Viral Diarrhea Virus Is through an Interferon Regulatory Factor 3-Dependent Mechanism

2002 ◽  
Vol 76 (18) ◽  
pp. 8979-8988 ◽  
Author(s):  
Susan J. Baigent ◽  
Gang Zhang ◽  
Martin D. Fray ◽  
Helen Flick-Smith ◽  
Stephen Goodbourn ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Bovine Viral Diarrhea Virus ◽  
Interferon Regulatory Factor ◽  
Bovine Viral Diarrhea ◽  
Regulatory Factor ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Nuclear Extracts ◽  
Infected Cells ◽  
Viral Diarrhea Virus

ABSTRACT 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.

Differential Expression of the Type I Interferon Pathway during Persistent and Transient Bovine Viral Diarrhea Virus Infection

2009 ◽  
Vol 29 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Megan L. Shoemaker ◽  
Natalia P. Smirnova ◽  
Helle Bielefeldt-Ohmann ◽  
Kathleen J. Austin ◽  
Alberto van Olphen ◽  
...  
Keyword(s):  
Virus Infection ◽  
Differential Expression ◽  
Bovine Viral Diarrhea Virus ◽  
Type I Interferon ◽  
Bovine Viral Diarrhea ◽  
Type I ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Interferon Pathway ◽  
Viral Diarrhea Virus

Acute non-cytopathic bovine viral diarrhea virus infection induces pronounced type I interferon response in pregnant cows and fetuses

2008 ◽  
Vol 132 (1-2) ◽  
pp. 49-58 ◽  
Author(s):  
Natalia P. Smirnova ◽  
Helle Bielefeldt-Ohmann ◽  
Hana Van Campen ◽  
Kathleen J. Austin ◽  
Hyungchul Han ◽  
...  
Keyword(s):  
Virus Infection ◽  
Bovine Viral Diarrhea Virus ◽  
Type I Interferon ◽  
Interferon Response ◽  
Bovine Viral Diarrhea ◽  
Type I ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

scholarly journals Upregulation of the type I interferon pathway in feedlot cattle persistently infected with bovine viral diarrhea virus

2020 ◽  
Vol 278 ◽  
pp. 197862 ◽  
Author(s):  
Sara M. Nilson ◽  
Aspen M. Workman ◽  
David Sjeklocha ◽  
Bruce Brodersen ◽  
Dale M. Grotelueschen ◽  
...  
Keyword(s):  
Bovine Viral Diarrhea Virus ◽  
Type I Interferon ◽  
Feedlot Cattle ◽  
Bovine Viral Diarrhea ◽  
Type I ◽  
Persistently Infected ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Interferon Pathway ◽  
Viral Diarrhea Virus

scholarly journals Transcriptomic analysis of bovine monocytes in response to non-cytopathic bovine viral diarrhea virus infection

2019 ◽  
Author(s):  
Yanhua HE ◽  
Yajun YANG ◽  
Xin HUANG ◽  
Yunfen ZHANG ◽  
Chencheng XIAO ◽  
...  
Keyword(s):  
Immune Response ◽  
Bovine Viral Diarrhea Virus ◽  
Immune Suppression ◽  
Type I Interferon ◽  
Bovine Viral Diarrhea ◽  
Type I ◽  
Interferon Signaling ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

Abstract Background: Monocytes are significant players in the detection of invading pathogens, particularly in pathogen defense. Bovine Viral Diarrhea Virus (BVDV) can cause a persistent infection and immune suppression if animals are infected with an non-cytopathic (ncp) biotype. However, its exact role in ncp BVDV-infected bovine monocytes remains poorly understood. To explore the immune suppression mechanisms of ncp BVDV, we used a transcriptomics approach to find genes with differential expression patterns in monocytes during infection with ncp BVDV over time. Results: Bovine monocytes were sampled at 2 and 24 h post-infection (hpi) to represent the early and late stages of an ncp biotype strain of bovine viral diarrhea virus infection. Compared with the non-infected cells, 9959 and 7977 differentially expressed gene (DEGs) were identified at 2 and 24 h hpi, respectively. These DEGs were associated with signal transduction, immune response, apoptotic process, cellular process , binding and cellular component. The differential expression profiles of select the type I interferon signaling pathway , interferon (IFN)-stimulated genes (ISGs), and genes involved in the innate immune response, including IRF7, DDX3X, TLR13, DDX58(RIG-I), MVAS, TLR9, TRAF6, IRF1, IFIT1, STAT1, ISG20, TRIM25, MX1,NLRX1, CYLD, SIKE1 and ZAP70 were confirmed by real-time quantitative PCR and consistent with the RNA-seq data. These results indicated that infection with ncp BVDV could activate type I interferon signaling pathway in bovine monocytes and induces weak ISGs responses, which extends our present understanding how the virus modulates the immune response and leads to better understanding behind the immunopathogenesis of ncp BVDV. Conclusion: Our transciptome anslysis provides useful initial data towards better understanding of the infection mechanisms used by ncp BVDV, while highlighting the potential molecular relationships occurring between the virus and the host’s immune response.

scholarly journals The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3

2007 ◽  
Vol 88 (11) ◽  
pp. 3002-3006 ◽  
Author(s):  
Julian Seago ◽  
Louise Hilton ◽  
Elizabeth Reid ◽  
Virginie Doceul ◽  
Janan Jeyatheesan ◽  
...  
Keyword(s):  
Bovine Viral Diarrhea Virus ◽  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Interferon Regulatory Factor ◽  
Bovine Viral Diarrhea ◽  
Regulatory Factor ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Infected Cells ◽  
Viral Diarrhea Virus

Classical swine fever virus (CSFV) is a member of the genus Pestivirus in the family Flaviviridae. The Npro product of CSFV targets the host's innate immune response and can prevent the production of type I interferon (IFN). The mechanism by which CSFV orchestrates this inhibition was investigated and it is shown that, like the related pestivirus bovine viral diarrhea virus (BVDV), this involves the Npro protein targeting interferon regulatory factor-3 (IRF-3) for degradation by proteasomes and thus preventing IRF-3 from activating transcription from the IFN-β promoter. Like BVDV, the steady-state levels of IRF-3 mRNA are not reduced markedly by CSFV infection or Npro overexpression. Moreover, IFN-α stimulation of CSFV-infected cells induces the antiviral protein MxA, indicating that, as in BVDV-infected cells, the JAK/STAT pathway is not targeted for inhibition.

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