Outcome of bovine herpesvirus 4 infection following direct viral injection in the lateral ventricle of the mouse brain

Donofrío, Gaetano; Cavaggioni, Andrea; Bondı̀, Michela; Cavirani, S.; Flammini, C. F.; Mucignat‐Caretta, Carla

doi:10.1016/j.micinf.2005.10.016

Cited by 25 publications

(26 citation statements)

References 37 publications

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“…BoHV-4-A, BAC-BoHV-4-A, BAC-BoHV-4-A-CMV-IgK-gE2gD-TM, BoHV-4-EFGP⌬TK, BoHV-1 (strain Oregon), and BVDV (strain NADL) were propagated by infecting confluent monolayers of MDBK or BEK cells at a multiplicity of infection (MOI) of 0.5 50% tissue culture infectious doses (TCID 50 ) per cell and maintained in minimal essential medium (MEM; Sigma) with 2% FBS for 2 h. The medium was then removed and replaced with fresh MEM containing 10% FBS. When approximately 90% of the cell monolayer exhibited cytopathic effect (CPE) (72 h postinfection), the virus was prepared by freezing and thawing cells three times and pelleting the virions through 30% sucrose, as described previously (3). Virus pellets were resuspended in cold MEM without FBS.…”

Section: Cellsmentioning

confidence: 99%

Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development

Donofrío¹,

Franceschi²,

Capocefalo³

et al. 2009

Clin Vaccine Immunol

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In a previous study, an apathogenic strain of bovine herpesvirus 4 (BoHV-4) cloned as a bacterial artificial chromosome and expressing a chimeric peptide (gE2/gD) as a secreted form was described. Recombinant virus-inoculated animals produced antibodies against bovine viral diarrhea virus (BVDV) gE2 and BoHV-1 gD. However, neutralizing antibodies were produced only against BVDV, not against BoHV-1. In the present work a recombinant BoHV-4 expressing a membrane-linked form of gE2/gD chimeric peptide was constructed, and inoculated rabbits produced serum-neutralizing antibodies against both BVDV and BoHV-1. Protein cell sorting and targeting are a very important issue when immunodominant antigens are engineered for recombinant virus vaccine development.

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Section: Cellsmentioning

confidence: 99%

Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development

Donofrío¹,

Franceschi²,

Capocefalo³

et al. 2009

Clin Vaccine Immunol

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“…Recombinants BoHV-4, wild-type BoHV-4 (strain LVR), and wildtype BoHV-1 (strain New York) were propagated by infecting confluent monolayers of Madin-Darby bovine kidney (MDBK) cells at a multiplicity of infection (MOI) of 0.5 50% tissue culture infectious doses (TCID 50 ) per cell and maintained in minimal essential medium (MEM) with 2% fetal bovine serum (FBS) for 2 h. The medium was then removed and replaced by fresh MEM containing 10% FBS. When approximately 90% of the cell monolayer exhibited CPE (approximately 72 h postinfection), the virus was prepared by freezing and thawing cells three times and pelleting the virions through 30% sucrose, as described previously (7). Virus pellets were resuspended in cold MEM without FBS.…”

Section: Methodsmentioning

confidence: 99%

“…BoHV-1 is known to play an important role in the bovine respiratory disease complex, commonly referred to as shipping fever (39). Inflammation and necrosis of respiratory epithelia and immunosuppression often lead to increased susceptibility to secondary viral and bacterial infections, resulting in severe clinical disease.Due to its biological characteristics, BoHV-4 has been suggested as a gene delivery vector (7,9,14). In the present work, we explored the feasibility of employing BoHV-4 as a vector to deliver the immunodominant glycoprotein D (gD) of BoHV-1 and generated a model for BoHV-1 vaccination by BoHV-4 expressing BoHV-1 gD.…”

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Recombinant Bovine Herpesvirus 4 (BoHV-4) Expressing Glycoprotein D of BoHV-1 Is Immunogenic and Elicits Serum-Neutralizing Antibodies against BoHV-1 in a Rabbit Model

Donofrío

Cavirani

Vanderplasschen

et al. 2006

Clin Vaccine Immunol

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Several biological characteristics of bovine herpesvirus 4 (BoHV-4) make it a good candidate as a gene delivery vector for vaccination purposes. These characteristics include little or no pathogenicity, unlikely oncogenicity, the capability to accommodate large amounts of foreign genetic material, the ability to infect several cell types coming from different animal species, and the ability to maintain transgene expression in both undifferentiated and differentiated cells. Bovine herpesvirus 4 (BoHV-4) has been isolated from a variety of samples and cells from healthy cattle and from cattle that have experienced abortion or with metritis, pneumonia, diarrhea, respiratory infection, and mammary pustular dermatitis (reviewed in reference 35). The virus was first isolated in Europe from cattle with respiratory and ocular diseases by Bartha et al. (2) and later in the United States by Mohanty et al. (26). Subsequently, distinct BoHV-4 isolates were obtained both in Europe and in the United States (11,25,31,34). However, the pathogenic role of BoHV-4 remains unclear, and only a few investigators have successfully produced an experimental disease (reviewed in reference 35). Although BoHV-4 is classified as a gammaherpesvirus based on genome sequence (3, 13, 41), it differs from other Gammaherpesviridae members in important biological properties. Unlike most other gammaherpesviruses, BoHV-4 causes cytopathic effect (CPE) and replicates in a variety of primary cultures and cell lines of bovine and various other animal species (32). In addition, there is no evidence for oncogenicity or growth transformation by BoHV-4.In contrast to BoHV-4, BoHV-1, an alphaherpesvirus, is a major viral pathogen of cattle and causes significant economic losses worldwide (39). Infection is accompanied by various clinical manifestations, such as infectious bovine rhinotracheitis, infectious pustular vulvovaginitis, balanoposthitis, abortion, and generalized systemic infection. BoHV-1 is known to play an important role in the bovine respiratory disease complex, commonly referred to as shipping fever (39). Inflammation and necrosis of respiratory epithelia and immunosuppression often lead to increased susceptibility to secondary viral and bacterial infections, resulting in severe clinical disease.Due to its biological characteristics, BoHV-4 has been suggested as a gene delivery vector (7,9,14). In the present work, we explored the feasibility of employing BoHV-4 as a vector to deliver the immunodominant glycoprotein D (gD) of BoHV-1 and generated a model for BoHV-1 vaccination by BoHV-4 expressing BoHV-1 gD. MATERIALS AND METHODSViruses. Recombinants BoHV-4, wild-type BoHV-4 (strain LVR), and wildtype BoHV-1 (strain New York) were propagated by infecting confluent monolayers of Madin-Darby bovine kidney (MDBK) cells at a multiplicity of infection (MOI) of 0.5 50% tissue culture infectious doses (TCID 50 ) per cell and maintained in minimal essential medium (MEM) with 2% fetal bovine serum (FBS) for 2 h. The medium was then removed and replac...

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“…When approximately 90% of the cell monolayer exhibited cytopathic effect (CPE) (72 h post infection), the virus was prepared by freezing and thawing cells three times and pelleting the virions through 30% sucrose, as described previously [27]. Virus pellets were resuspended in cold MEM without FBS.…”

Section: Introductionmentioning

confidence: 99%

Virus-Mediated Metalloproteinase 1 Induction Revealed by Transcriptome Profiling of Bovine Herpesvirus 4-Infected Bovine Endometrial Stromal Cells

Tebaldi

Jacca

Montanini

et al. 2016

Biology of Reproduction

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Viral infections can cause genital tract disorders (including abortion) in cows, and bovine herpesvirus 4 (BoHV-4) is often present in endometritis-affected animals. A major problem with cattle uterine viral infections in general, and BoHV-4 in particular, is our limited understanding of the pathogenic role(s) that these infections play in the endometrium. A similar lack of knowledge holds for the molecular mechanisms utilized, and the host cell pathways affected, by BoHV-4. To begin to fill these gaps, we set up optimized conditions for BoHV-4 infection of a pure population of bovine endometrial stromal cells (BESCs) to be used as source material for RNA sequencing-based transcriptome profiling. Many genes were found to be upregulated (417) or downregulated (181) after BoHV-4 infection. As revealed by enrichment functional analysis on differentially expressed genes, BoHV-4 infection affects various pathways related to cell proliferation and cell surface integrity, at least three of which were centered on upregulation of matrix metalloproteinase 1 (MMP1) and interleukin 8 (IL8). This was confirmed by reverse transcription PCR, real-time PCR, Western-immunoblot analysis, and a luciferase assay with a bovine MMP1-specific promoter reporter construct. Further, it was found that MMP1 transcription was upregulated by the BoHV-4 transactivator IE2/RTA, leading to abnormally high metalloproteinase tissue levels, potentially leading to defective endometrium healing and unresolved inflammation. Based on these findings, we propose a new model for BoHV-4 action centered on IE2-mediated MMP1 upregulation and novel therapeutic interventions based on IFN gamma-mediated MMP1 downregulation.

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Outcome of bovine herpesvirus 4 infection following direct viral injection in the lateral ventricle of the mouse brain

Cited by 25 publications

References 37 publications

Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development

Cellular Targeting of Engineered Heterologous Antigens Is a Determinant Factor for Bovine Herpesvirus 4-Based Vaccine Vector Development

Recombinant Bovine Herpesvirus 4 (BoHV-4) Expressing Glycoprotein D of BoHV-1 Is Immunogenic and Elicits Serum-Neutralizing Antibodies against BoHV-1 in a Rabbit Model

Virus-Mediated Metalloproteinase 1 Induction Revealed by Transcriptome Profiling of Bovine Herpesvirus 4-Infected Bovine Endometrial Stromal Cells

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