Progress 09/01/15 to 08/31/18
Outputs
Target Audience:The target audience included undergraduate students, graduate students, faculty members, virologists, pharmaceutical companies interested in animal vaccines, and neuroscientists. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?During the course of this grant, one graduate student received her Ph.D. and one who is working on Objective 3 is in the middle of his Ph.D. Also, a graduate student from Egypt who is a visiting scholar in my lab also worked on studies in Objective 3. A postdoctoral fellow in my lab also worked on Objective 1 and 2. Two visiting scholars from China also contributed to our studies described in Objectives 1 and 2. How have the results been disseminated to communities of interest?Publications in peer-reviewed journals, as summarized above, are an important means of disseminating findings from ourstudies. The graduate students, postdocs, and visiting scientists have given talks at the International Herpesvirus workshop and American Society of Virology. I have also given talks at the Nebraska Center for Virology Intercampus Meeting in 2017, University of California-Irvine, University of Colorado, and Colorado alpha-herpesvirus Symposium, Viral Pathogenesis Symposium, Eastern Virginia Medical School, European Veterinary Herpesvirus Symposium in Ghent, Belgium. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Objective 1: Perform structure-function analysis of ORF2. We found that a viral protein expressed during latency (ORF2) is associated with two cellular proteins (HMGA1 and beta-catenin). HMGA1 and beta-catenin regulate the Wnt signaling pathway, protect neurons from cell death, promote axonal growth, and promote synaptic connections. We believe that the ability of ORF2 to interact with beta-catenin and HMGA1 is crucial for maintaining a latent infection. We are currently exploring whether ORF2 and beta-catenin are both associated with a promoter that is stimulated by beta-catenin. The results from these studies were published in 2 Journal of Virology publications. Objective 2: Identify viral protein expressed during the escape from latency. We developed peptide-specific antibodies that specifically interact with two important viral regulatory proteins (bICP4 and bICP22). These antibodies were affinity purified and used to test whether these viral proteins are expressed during early stages of reactivation from latency. We recently demonstrated that bICP4 and bICP22 are expressed during reactivation from latency. These studies were recently submitted to the Journal of Neurovirology for publication. Objective 3: Compare viral RNA expression during the escape from latency to productive infection. We have identified more than 100 Wnt-responsive genes by RNA-seq studies that are differentially expressed in trigeminal calves (TG) of calves that are latently infected versus the same tissue from uninfected calves or during early stages of reactivation from latency. These studies revealed that Wnt agonists are expressed at higher levels during latency relative to uninfected calves or during reactivation from latency. During stress-induced reactivation from latency, we found that Wnt agonists are induced in TG. Strikingly, several of these Wnt antagonists are also expressed at higher levels in neurons of patients suffering from Alzheimer's Disease or Parkinsons Disease adding support to our conclusions that expression of these proteins during reactivation from latency is detrimental to maintaining a latent infection. These studies are paradigm shifting because it is known that the Wnt signaling pathway is important for axonal growth, neuronal survival, and repair of damaged axons, all features crucial for maintaining a life-long latent infection. Interestingly, these studies also determined that the mTOR pathway, which is involved in HSV-1 reactivation from latency, is tightly regulated during the bovine herpesvirus 1 (BoHV-1) latency-reactivation cycle. We are still analyzing the RNA-Seq data to uncover other signaling pathways that are differentially regulated during the latency-reactivation cycle. Interestingly, we also found that the Wnt pathway is important for efficient productive infection. Although this may seem contradictory to the conclusion that Wnt supports maintenance of latency, it is known that Wnt has tissue and cell-specific functions suggesting in neurons the Wnt pathways maintains latency but in non-neuronal cells, it can promote viral replication. Three manuscripts focused on this objective were published in the Journal of Virology and 1 in Virology. Objective 4: Examine the effect stress has on viral transcription and productive infection. Using RNA-seq approaches we have identified viral genes that are stimulated by the synthetic corticosteroid dexamethasone during productive infection. One of these viral genes is bICP4, which we previously demonstrated contains a promoter that is stimulated by dexamethasone. Surprisingly, these studies also demonstrated that several late viral genes were stimulated by dexamethasone. Dexamethasone and infection were found to activate a cellular protein kinase (Akt) that regulates cell survival. An independent study demonstrated that a cellular protein kinase regulated by stress (SGK) is also induced by dexamethasone and infection. We also have found that a mouse neuroblastoma cell line (Neuro-2A) supportslow levels of virus production and dexamethasone stimulates productive infection suggesting this may be a useful model to examine virus-host interactions. Recent studies demonstrated that the BoHV-1 immediate early transcription unit 1 (IEtu1) promoter, which drives expression of important viral transcriptional regulators (bICP0 and bICP4), which contains two functional glucocorticoid receptor (GR) response elements (GREs) is stimulated by the synthetic corticosteroid dexamethasone. A stress-induced transcription factor, Krüppel-like transcription factor 15 (KLF15), cooperates with the GR to stimulate productive infection as well as the IEtu1 promoter. Interestingly, we also found that the host cell factor 1 (HCF-1) is critical for GR activation of the viral IEtu1 promoter and suggest that an HCF-1-GR complex can stimulate the IEtu1 promoter in the absence of the viral IE activator VP16. Collectively, these studies have provided new insight into the mechanisms by which stress regulates viral replication and reactivation from latency. Studies from this objective lead to 3 manuscripts published in the Journal of Virology, 3 in Virology, and 2 in Virus Research.
Publications
- Type:
Journal Articles
Status:
Awaiting Publication
Year Published:
2018
Citation:
Sawant, L., I. Kook, J.L. Vogel, T.M. Kristie, and C. Jones. The cellular coactivator HCF-1 is required for glucocorticoid receptor-mediated transcription of bovine herpesvirus 1 immediate early genes. J of Virology, IN PRESS.
- Type:
Journal Articles
Status:
Awaiting Publication
Year Published:
2018
Citation:
The canonical Wnt/?-catenin signaling pathway stimulates herpes simplex virus 1 productive infection. Virus Res, IN PRESS
- Type:
Book Chapters
Status:
Published
Year Published:
2018
Citation:
El-mayet F.S., S.A. El-Habbaa, G.F. El-Bagoury, S.S.A. Sharawi, E.M. El-Nahas, and C. Jones. 2018. The glucocorticoid receptor and certain Kr�ppel-like transcription factors have the potential to synergistically stimulate bovine herpesvirus 1 transcription and reactivation from latency. In Transcriptional Regulation.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Zhu, L., C. Jones, and G. Zhang. 2018. The role of phospholipase C signaling in macrophage-mediated inflammatory response. J. of Immunology Research, Article ID 5201759.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Workman, A. L. Zhu, B.N. Keel, T.P.L. Smith, and C. Jones. The Wnt signaling pathway is differentially expressed during the bovine herpesvirus 1 latency-reactivation cycle: evidence that two protein kinases associated with neuronal survival (Akt3 and bone morphogenetic protein receptor 2) are expressed at higher levels during latency. 2018. J of Virology 92: e01937-17
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Progress 09/01/16 to 08/31/17
Outputs
Target Audience:Cattle ranchers, dairy cattle producers, bovine health specialists, herpes virologists, and virologists in general were reached during the last year. Changes/Problems:Objective 2: Identify viral protein expressed during the escape from latency. Two antibodies directed against viral regulatory proteins (bICP4 and bICP22) worked well in Western Blot assays, but did not work well in immunohistochemistry studies. Consequently, we are producing new antibodies directed against these important viral regulatory proteins. These antibodies will be affinity purified and thus should work better than the crude antiserum we previously used. These antibodies will be utilized to examine viral protein expression during early stages of reactivation from latency. Objective 3: Compare viral RNA expression during the escape from latency to productive infection. We found that identifying low levels of viral gene expression during reactivation from latency is difficult. We will use a new strategy, NimbleGen SeqCap Target Enrichment (Roche) for Next Generation Sequencing. This strategy will allow us to target viral genes, thus allowing identification of viral mRNAs that are induced during early stages of reactivation from latency. An alternative strategy will be concurrently performed: we will develop primers for specific viral transcripts that regulate productive infection and perform qRT-PCR to test whether these viral transcripts are expressed during reactivation from latency. The viral genes that will be analyzed by qRT-PCR include: all viral immediate early mRNAs (bICP4, bICP0, and bICP22), early mRNAs that regulate viral DNA replication (thymidine kinase, ribonucleotide reductase, thymidylate kinase, dUTPase, DNA polymerase, and origin binding protein), and certain late genes (VP16, gB, gC, and gD). What opportunities for training and professional development has the project provided?Many of these studies have been performed by a post-doctoral fellow and graduate student in my lab. These studies are very important for their training and professional development. How have the results been disseminated to communities of interest?Publications in peer-reviewed journals, as summarized above, are am important means of disseminating findings from our studies. The postdoc and I gave talks at the International Herpesvirus workshop last year. I also gave a talk at the Nebraska Center for Virology Intercampus Meeting in 2017 (March, 2017), University of California-Irvine (April 2017), and Colorado alpha-herpesvirus Symposium (May 2017). I will also present talks at the Viral Pathogenesis Symposium, Eastern Virginia Medical School (June 24th, 2017), European Veterinary Herpesvirus Symposium (July 29, 2017 in Gehnt, Belgium), and at the International Herpesvirus Workshop (August 1, 2017 in Ghent, Belgium). What do you plan to do during the next reporting period to accomplish the goals?Studies in Objective 2: Identify viral protein expressed during the escape from latency have not completed. The reason these studies were not completed is two antibodies directed against viral proteins (bICP4 and bICP22) work well in Western Blot assays, but yield high background in immunohistochemistry (IHC) studies. Thus, the bICP4 and bICP22 antibodies are not suitable for IHC studies. Consequently, we are producing new antibodies directed against these important viral regulatory proteins. These antibodies will be affinity purified and thus should work better than the crude antiserum we previously used. These antibodies will be used to examine viral protein expression during early stages of reactivation from latency. Studies in Objective 3: Compare viral RNA expression during the escape from latency to productive infection, were not completed. We are finding that identifying low levels of viral gene expression during reactivation from latency is difficult. We will use a new strategy, NimbleGen SeqCap Target Enrichment (Roche) for Next Generation Sequencing. This strategy will allow us to target viral genes, thus allowing identification of viral mRNAs that are induced during early stages of reactivation from latency. An alternative strategy will be concurrently performed: we will develop primers for specific viral transcripts that regulate productive infection and perform qRT-PCR to test whether these viral transcripts are expressed during reactivation from latency. The viral genes that will be analyzed by qRT-PCR include: all viral immediate early mRNAs (bICP4, bICP0, and bICP22), early mRNAs that regulate viral DNA replication (thymidine kinase, ribonucleotide reductase, thymidylate kinase, dUTPase, DNA polymerase, and origin binding protein), and certain late genes (VP16, gB, gC, and gD).
Impacts
What was accomplished under these goals?
Objective 1: We have found that a viral protein expressed during latency (ORF2) is associated with two cellular proteins (HMGA1 and beta-catenin). HMGA1 and beta-catenin regulate the Wnt signaling pathway, protect neurons from cell death, promote axonal growth, and promote synaptic connections. We believe that the ability of ORF2 to interact with beta-catenin and HMGA1 is crucial for maintaining a latent infection. Objective 3: We have identified Wnt responsive genes, by RNA-seq studies, that are expressed during the latency-reactivation cycle and are in the process of verifying that these genes are differentially regulated. Interestingly, these studies also determined that the mTOR pathway, whcih is involved with HSV-1 reactivation from latency, is tightly regulated during the bovine herpesvirus 1 (BoHV-1) latency-reactivation cycle. Objective 4: Using RNA-seq appraoches we have identified viral genes that are stimulated by the synthetic corticostroid dexamethasone during productive infection. One of these viral genes is bICP4, whcih we previously demonstrated contains a promoter that is stimulated by dexamethasone. Surprisingly, these studies also demonstrated that several late viral genes were stimulated by dexamethasone. Dexamethasone and infection were found to activate a cellular protein kinase (Akt) that regulates cell survival. An independent study demonstrated that a cellular protein kinase regulated by stress (SGK) is also induced by dexamethasone and infection. Finally, we have found that a mouse neuroblastoma cell line (Neuro-2A) supports low levels of virus production and dexamethasone stimulates productive infection suggesting this may be a useful model to examine virus-host interactions. Collectively, these studies demonstrated that stress has many effects on viral replication.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Zhu, L, P. Thunuguntla , Y. Liu, M. Hancock, and C. Jones. 2017. The beta-catenin signaling pathway stimulates bovine herpesvirus 1 productive infection. Virology, 500: 91-95.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Thunuguntla, P., F. S. El-mayet, and C. Jones. 2017. Bovine herpesvirus 1 can efficiently infect the human (SH-SY5Y) but not the mouse neuroblastoma cell line (Neuro-2A). 232:1-5 Virus Res.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Zhu, L, J. Thompson, F. Ma, J. Eudy, and C. Jones. 2017. Effects of the synthetic corticosteroid dexamethasone on bovine herpesvirus 1 productive infection. Virology:, 505: 71-79.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Zhu, L., A. Workman, and C. Jones. 2017. A potential role for a beta-catenin coactivator (high mobility group AT-hook 1 protein) during the latency-reactivation cycle of bovine herpesvirus 1. J of Virology: 91: e02132-16
- Type:
Journal Articles
Status:
Accepted
Year Published:
2017
Citation:
Zhu, L. and C. Jones. The high mobility group AT-hook 1 protein stimulates bovine herpesvirus 1 productive infection. IN PRESS, Virus Res
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Progress 09/01/15 to 08/31/16
Outputs
Target Audience:Virologists, immunologists, ranchers, veterinarians, pharmaceutical companies, and animal vaccine companies. Changes/Problems:We have found that identifying low levels of viral gene expression during reactivation from latency is difficult. We will use new strategies for Next Generation Sequencing that will target viral genes to try and identify the viral mRNAs that are stimulated during initial stages of reactivation from latency. Our antibodies directed against bICP4 and bICP22 work well in Western blots, but exhibit too much background in immuno-histochemistry studies. Consequently, we are developing better antibodies directed against these proteins to test whether they are expressed during early stages of reactivation from latency. What opportunities for training and professional development has the project provided?A graduate student in my laboratory, Insun Kook performed the studies described for Objective 4. A postdoc (Yilin Liu), a visiting scientist (Liqian Zhu), and a techinician (Prasanth Thunuguntla) have performed the other studies described above. How have the results been disseminated to communities of interest?Several of these studies have been published in peer-reviewed journals or they are in press, as described above. In July 2016, the postdoc and I gave talks at the International Herpesvirus Workshop in Madison WI . At this meeting, we also presented posters. The titles of these talks are: 1. Regulation of beta-catenin, a transcription factor activated by canonical Wnt signaling, by bovine herpesvirus 1 during the latency-reactivation cycle. Presented by Dr Liqian Zhu 2. Stress mediated trans-activation of the BoHV-1 immediate early transcription unit 1 promoter is enhanced by the transcriptional coactivator, Host Cell Factor-1. During 2016, the PD presented additional presentations, whcih are listed below: 1. 1/25/2016: Jones, C. Towards an understanding of the latency-reactivation cycle of Alphaherpesviruses. Departmental Seminar. University of Colorado Health Science Center, January 25, 2016. 2. 3/20/2016. Jones, C. Regulation of beta-catenin, a transcription factor activated by canonical Wnt signaling, by bovine herpesvirus 1. Nebraska Center for Virology Intercampus Meeting. 3. 5/12/2016: The canonical Wnt/ beta-catenin signaling pathway is active in in sensory neurons of calves latently infected with bovine herpesvirus 1. Colorado alpha-herpesvirus Latency Symposium. What do you plan to do during the next reporting period to accomplish the goals?We will prepare manuscirpts focused on ORF2 and b-catenin, the ability of stress to simtulate viral gene expression, and stress-mediated activation of bICP4. In addition, the following studies will be performed: Objective 2: Identify viral proteins expressed during the escape from latency. We are currently preparing additional antibodies directed against two additional viral transcriptional regulatory proteins (bICP4 and bICP22). These will be used to examine expression of bICP4 and bICP22 during early stages of reactivation from latency. Objective 3: Compare viral RNA expression during the escape from latency to productive infection. Although RNA-seq studies have identified cellular transcripts that are differentially expressed during reactivation from latency, we have not identified viral transcripts becuase they are expressed at low levels during reactivation. Consequently, we will test whether we can enrich for viral transcripts and then perform RNA-Seq studies. If that approach is not successful, we will perform quantiative RT-PCR to determine if viral mRNA that encodes viral regulatory proteins are expressed during early stages of reactivation. Objective 4: Examine the effect stress has on viral transcription and productive infection. We are testing other regions of the BoHV-1 genome that contain glucocorticoid receoptor binding sites for their ability to be regulated by dexamethasone. We are also examining the effects of cellular transription factors to cooperate with the glucocorticoid receptor and activate viral transcription.
Impacts
What was accomplished under these goals?
Studies Related to Objective 1: beta-catenin, a transcription factor activated by the canonical Wnt signaling pathway was frequently detected in ORF2+ trigeminal ganglionic neurons of latently infected, but not mock-infected calves. Conversely, the lytic cycle regulatory protein (bICP0) was not frequently detected in b-catenin+ neurons in latently infected calves. During dexamethasone-induced reactivation from latency, mRNA expression levels of two Wnt antagonists, dickkopf1 (DKK1) and secreted frizzled protein 2 (SFRP2), were induced in bovine TG, which correlated with reduced b-catenin protein expression in TG neurons six hours after dexamethasone treatment. The Wnt signaling pathway interferes with neuro-degeneration but promotes neuronal differentiation suggesting stabilization of b-catenin expression by ORF2 promotes neuronal survival and differentiation, which is crucial for maintaining latency. ORF2 inhibits apoptosis, interacts with Notch family members, and interferes with Notch-dependent transcription suggesting ORF2 expression enhances survival of infected neurons. The Notch signaling pathway is crucial for neuronal differentiation and survival suggesting that interactions between ORF2 and Notch family members regulate certain aspects of latency. In a recent study, we compared whether ORF2 interfered with the four mammalian Notch family members. ORF2 consistently interfered with Notch1-3-mediated transactivation of three cellular promoters. Conversely, Notch4-mediated transcription was not consistently inhibited by ORF2. Electrophoretic shift mobility assays using four copies of a consensus-DNA binding site for Notch/CSL (core binding factor (CBF)-1, Suppressor of Hairless, Lag-2) as a probe revealed ORF2 interfered with Notch1 and 3 interactions with a CSL family member bound to DNA. These studies indicate that ORF2 inhibits Notch-mediated transcription and signaling by interfering with Notch interacting with CSL bound to DNA. These studies are approximately 65% completed. The impact of accomplishments of these studies are summarized below. First, ORF2 is expressed in latently infected neurons and plays a crucial role in the latency-reactivation. Consequently, understanding the mechanism by which ORF2 regulates the latency-reactivation cycle provides new therapeutic approaches to control the latency-reactivation cycle in cattle, including new vaccines. Secondly, the ability of ORF2 to regulate two crucial cellular signaling pathways (Wnt and Notch) are paradigm changing discoveries and may have therpaeutic value. For example, Wnt and Notch regulate tumor growth and neurogenesis. Perhaps ORF2 can be used as a anti-tumor agent or used to stimulate neurogenesis. In the context of "One Health", these are intriguing findings that may benefit human and animal health. This objective has been completed. Studies related to Objective 2: Bovine herpesvirus 1 (BoHV-1) establishes latency in sensory neurons. The synthetic corticosteroid dexamethasone consistently induces reactivation from latency making it an interesting model to study the events that lead to reactivation from latency. a previous study demonstrated that within 90 min after latently infected calves are treated with dexamethasone,two BHV-1 regulatory proteins, BHV-1-infected cell protein 0 (bICP0) and viral protein 16 (VP16), are expressed in the same neuron. Additional studies demonstrated that VP16 and bICP0 can be detected at 22 and 33 min after dexamethasone (DEX) treatment of latently infected calves. However, we were unable to discern whether VP16 or bICP0 was expressed at early times after reactivation. VP16+ neurons consistently express the glucocorticoid receptor suggesting corticosteroid-mediated activation of its receptor rapidly stimulates reactivation from latency. These studies are 75% complete. The impact of studies in this objective is these studies provide evidence that bICP0 and VP16 regulate early stages of reactivation. Consequently, novel vaccines may be possible to develop in which bICP0 and/or VP16 are mutated to prevent reactivation from latency. We are preparing an additional antibody against bICP4 and bICP22 to test whether it is expressed during reactivation from latency. These viral proteins are very important because like bICP0 they are transcriptional regulatory proteins and are expressed very early during infection. This objective is approximately 66% completed. Studies related to Objective 3: During productive infection, we have demonstrated that RNA and protein expression of a viral transcriptional factor (bICP4) is stimulated by the synthetic corticosteroid dexamethasone. Additional studies are examining the effect of dexamethasone on additional viral genes that were stimulated by dexamethasone. Interestingly, dexamethasone stimulated expression of several late genes, suggesting these genes must be expressed during early stages of reactivation from latency. The impact of the findings in this objective is: these studies provides the first evidence that stress, as mimicked by the synthetic corticosteroid dexamethasone, stimulates viral transcription. Consequently, these findings may lead to novel therpaeutic strategies that can interfere with reactivation from latency following a stressful stimulus. The studies in this objective are approximately 60% completed. Studies related to Objective 4:The primary site for life-long latency of bovine herpesvirus 1 (BHV-1) is sensory neurons. The synthetic corticosteroid dexamethasone consistently induces reactivation from latency; however the mechanism by which corticosteroids mediate reactivation is unclear. In this study, we demonstrate for the first time that dexamethasone stimulates productive infection, in part, because the BHV-1 genome contains more than 100 potential glucocorticoid receptor (GR) response elements (GREs). Immediate early transcription unit 1 (IEtu1) promoter activity, but not IEtu2 or VP16 promoter activity, was stimulated by dexamethasone. Two near perfect consensus GREs located within the IEtu1 promoter are necessary for dexamethasone-mediated stimulation. Electrophoretic mobility shift assays and chromatin immunoprecipitation studies demonstrated that the GR interacts with IEtu1 promoter sequences containing the GREs. Serum and glucocorticoid-regulated protein kinases (SGK) are serine/threonine protein kinases that contain a catalytic domain resembling other protein kinases: AKT/protein kinase B, protein kinase A, and protein kinase C-Zeta for example. Unlike these constitutively expressed protein kinases, SGK1 RNA and protein levels are increased by growth factors and corticosteroids. Stress can directly stimulate SGK1 levels as well as stimulate BHV-1 productive infection and reactivation from latency suggesting SGK1 can stimulate productive infection. A specific SGK inhibitor (GSK650394) significantly reduced BHV-1 replication in cultured cells. Proteins encoded by the three BoHV-1 immediate early genes (bICP0, bICP4, and bICP22) and two late proteins (VP16 and gE) were consistently reduced by GSK650394 during early stages of productive infection. The studies in this objective are 65% completed. The impacts of findings in this objective are for the first time we have demonstrated that GREs in the BHV-1 genome are functional and the SGK protein kinase stimulates viral infection. These findings also indicate that stress has pleotropic effects on BHV-1 replication. These studies are approximately 80% completed.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Kook, I. and C. Jones. 2016. The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection. Virus Res, 222:106-112.
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Liu, Y. and C. Jones. Regulation of Notch-mediated transcription by a bovine herpesvirus 1 encoded protein (ORF2) that is expressed in latently infected sensory neurons. Journal of Neurovirology.
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Liu, Y., M. Hancock, A. Workman, A. Doster, and C. Jones. 2016. beta-catenin, a transcription factor activated by canonical Wnt signaling, is expressed in sensory neurons of calves latently infected with bovine herpesvirus 1. Journal of Virology, 90:3148-3159.
- Type:
Book Chapters
Status:
Published
Year Published:
2016
Citation:
Jones. C. 2016. Latency of Bovine Herpesvirus 1 (BoHV-1) in Sensory Neurons. 2016. - ISBN 978-953-51-2611-9, edited by J. Ongradi, Herpesviridae237-261.
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Kook, I., C. Henley, F. Meyer, F.G. Hoffmann, and C. Jones. 2015. Bovine herpesvirus 1 productive infection and immediate early transcription unit 1 promoter are stimulated by the synthetic corticosteroid dexamethasone. Virology, 484:377-385
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Kook, I., A. Doster, and C. Jones. 2015. Bovine herpesvirus 1 regulatory proteins are detected in trigeminal ganglionic neurons during the early stages of stress-induced escape from latency. J Neurovirology 21: 585-591.
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