scholarly journals Cooperative Transformation and Coexpression of Bovine Papillomavirus Type 1 E5 and E7 Proteins

2001 ◽  
Vol 75 (1) ◽  
pp. 513-521 ◽  
Author(s):  
Joanna Bohl ◽  
Bruce Hull ◽  
Scott B. Vande Pol
Keyword(s):  
Epithelial Cells ◽  
Cellular Response ◽  
Ectopic Expression ◽  
Granular Cell ◽  
Bovine Papillomavirus ◽  
Basal Cells ◽  
Cultured Epithelial Cells ◽  
E5 Oncoprotein ◽  
E7 Proteins

ABSTRACT Productively infected bovine fibropapillomas were examined for bovine papillomavirus type 1 (BPV-1) E7 localization. BPV-1 E7 was observed in the cytoplasm of basal and lower spinous epithelial cells, coexpressed in the cytoplasm of basal cells with the E5 oncoprotein. E7 was also observed in nucleoli throughout the basal and spinous layers but not in the granular cell layer. Ectopic expression of E7 in cultured epithelial cells gave rise to localization similar to that seen in productive fibropapillomas, with cytoplasmic and nucleolar expression observed. Consistent with the coexpression of E7 and E5 in basal keratinocytes, BPV-1 E7 cooperated with E5 as well as E6 in an anchorage independence transformation assay. While E5 is expressed in both basal and superficial differentiating keratinocytes, BPV-1 E7 is only observed in basal and lower spinous epithelial cells. Therefore, BPV-1 E7 may serve to modulate the cellular response of basal epithelial cells to E5 expression.

scholarly journals Inoculation of young horses with bovine papillomavirus type 1 virions leads to early infection of PBMCs prior to pseudo-sarcoid formation

2011 ◽  
Vol 92 (10) ◽  
pp. 2437-2445 ◽  
Author(s):  
Bettina Hartl ◽  
Edmund K. Hainisch ◽  
Saeed Shafti-Keramat ◽  
Reinhard Kirnbauer ◽  
Annunziata Corteggio ◽  
...  
Keyword(s):  
Neutralization Assay ◽  
Bovine Papillomavirus ◽  
Serum Antibodies ◽  
Intact Skin ◽  
Papillomavirus Infection ◽  
E5 Protein ◽  
E5 Oncoprotein ◽  
Young Horses ◽  
And Control

Bovine papillomavirus types 1 and 2 (BPV-1 and BPV-2) are known to induce common equine skin tumours, termed sarcoids. Recently, it was demonstrated that vaccination with BPV-1 virus-like particles (VLPs) is safe and highly immunogenic in horses. To establish a BPV-1 challenge model for evaluation of the protective potential of BPV-1 VLPs, four foals were injected intradermally with infectious BPV-1 virions and with viral genome-based and control inocula, and monitored daily for tumour development. Blood was taken before inoculation and at weekly intervals. BPV-1-specific serum antibodies were detected by a pseudo-virion neutralization assay. Total nucleic acids extracted from tumours, intact skin and PBMCs were tested for the presence of BPV-1 DNA and mRNA using PCR and RT-PCR, respectively. Intralesional E5 oncoprotein expression was determined by immunofluorescence. Pseudo-sarcoids developed exclusively at sites inoculated with virions. Tumours became palpable 11–32 days after virion challenge, reached a size of ≤20 mm in diameter and then resolved in ≤6 months. No neutralizing anti-BPV-1 serum antibodies were detectable pre- or post-challenge. BPV-1 DNA was present in lesions but not in intact skin. In PBMCs, viral DNA was already detectable before lesions were first palpable, in concentrations correlating directly with tumour growth kinetics. PBMCs from two of two foals also harboured E5 mRNA. Immunofluorescence revealed the presence of the E5 protein in tumour fibroblasts, but not in the apparently normal epidermis overlying the lesions. Together with previous findings obtained in horses and cows, these data suggest that papillomavirus infection may include a viraemic phase.

scholarly journals Interaction of tSNARE Syntaxin 18 with the Papillomavirus Minor Capsid Protein Mediates Infection

2005 ◽  
Vol 79 (11) ◽  
pp. 6723-6731 ◽  
Author(s):  
Ioannis Bossis ◽  
Richard B. S. Roden ◽  
Ratish Gambhira ◽  
Rongcun Yang ◽  
Mitsuo Tagaya ◽  
...  
Keyword(s):  
Cell Surface ◽  
Capsid Protein ◽  
Ectopic Expression ◽  
Bovine Papillomavirus ◽  
Perinuclear Region ◽  
Minor Capsid Protein ◽  
Protein Receptor ◽  
Virion Morphogenesis ◽  
Target Membrane

ABSTRACT The papillomavirus capsid mediates binding to the cell surface and passage of the virion to the perinuclear region during infection. To better understand how the virus traffics across the cell, we sought to identify cellular proteins that bind to the minor capsid protein L2. We have identified syntaxin 18 as a protein that interacts with bovine papillomavirus type 1 (BPV1) L2. Syntaxin 18 is a target membrane-associated soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (tSNARE) that resides in the endoplasmic reticulum (ER). The ectopic expression of FLAG-tagged syntaxin 18, which disrupts ER trafficking, blocked BPV1 pseudovirion infection. Furthermore, the expression of FLAG-syntaxin 18 prevented the passage of BPV1 pseudovirions to the perinuclear region that is consistent with the ER. Genetic studies identified a highly conserved L2 domain, DKILK, comprising residues 40 to 44 that mediated BPV1 trafficking through the ER during infection via an interaction with the tSNARE syntaxin 18. Mutations within the DKILK motif of L2 that did not significantly impact virion morphogenesis or binding at the cell surface prevented the L2 interaction with syntaxin 18 and disrupted BPV1 infection.

scholarly journals Bovine Papillomavirus Type 2 Infection Associated with Papillomatosis of the Amniotic Membrane in Water Buffaloes (Bubalus bubalis)

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 262 ◽  
Author(s):  
Valeria Russo ◽  
Franco Roperto ◽  
Davide De Biase ◽  
Pellegrino Cerino ◽  
Chiara Urraro ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Amniotic Membrane ◽  
Squamous Metaplasia ◽  
Bubalus Bubalis ◽  
Productive Infection ◽  
Bovine Papillomavirus ◽  
Water Buffaloes ◽  
E5 Oncoprotein ◽  
Functional Complex

Multiple papillomatous nodules were observed scattered over the amniotic membrane in six water buffaloes that had recently aborted. Grossly, some of the nodules had multiple villous projections while others appeared as single prominent conical or cylindrical horns. Histology revealed folded hyperplastic and hyperkeratotic epithelium supported by a narrow fibro-vascular stalk. Using PCR, sequences of the bovine Deltapapillomavirus type 2 (BPV-2) E5 gene were amplified from the amniotic papillomas. Furthermore, expression of the E5 gene was detected using reverse transcription (RT)-PCR. Western blotting revealed BPV-2 E5 oncoprotein as well as L1 protein, suggesting both abortive and productive infection. Additionally, a functional complex composed of BPV-2 E5 oncoprotein and the phosphorylated PDGFβR was detected, which is consistent with the activation of PDGFβR by the interaction with BPV-2 E5 oncoprotein. These results demonstrate that BPV-2 can infect the amnion of water buffaloes and suggest that this infection may cause proliferation of the epithelial cells of the amnion. While the precise pathogenesis in uncertain, it is possible that BPV-2 infection of stratified squamous epithelial cells within squamous metaplasia foci and/or amniotic plaques could lead to papilloma formation. Papillomavirus-associated amniotic papillomas have not previously been reported in any species, including humans.

scholarly journals Vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of bovine papillomavirus type 1

2008 ◽  
Vol 89 (1) ◽  
pp. 148-157 ◽  
Author(s):  
G. H. Ashrafi ◽  
K. Piuko ◽  
F. Burden ◽  
Z. Yuan ◽  
E. A. Gault ◽  
...  
Keyword(s):  
Immune Response ◽  
Controlled Trial ◽  
Disease Process ◽  
Chimeric Virus ◽  
Tumour Regression ◽  
Bovine Papillomavirus ◽  
Virus Like Particles ◽  
Tumour Rejection ◽  
E7 Proteins

Equine sarcoids are fibroblastic skin tumours affecting equids worldwide. While the pathogenesis is not entirely understood, infection with bovine papillomavirus (BPV) type 1 (and less commonly type 2) has been implicated as a major factor in the disease process. Sarcoids very seldom regress and in fact often recrudesce following therapy. Nothing is known about the immune response of the equine host to BPV. Given that the viral genes are expressed in sarcoids, it is reasonable to assume that vaccination of animals against the expressed viral proteins would lead to the induction of an immune response against the antigens and possible tumour rejection. To this end we vaccinated sarcoid-bearing donkeys in a placebo-controlled trial using chimeric virus-like particles (CVLPs) comprising BPV-1 L1 and E7 proteins. The results show a tendency towards enhanced tumour regression and reduced progression in the vaccinated group compared to control animals. Although promising, further studies are required with larger animal groups to definitely conclude that vaccination with CVLPs is a potential therapy for the induction of sarcoid regression.

scholarly journals Upregulation of equine matrix metalloproteinase 1 by bovine papillomavirus type 1 is through the transcription factor activator protein-1

2011 ◽  
Vol 92 (11) ◽  
pp. 2608-2619 ◽  
Author(s):  
ZhengQiang Yuan ◽  
Elizabeth A. Gault ◽  
M. Saveria Campo ◽  
Lubna Nasir
Keyword(s):  
Transcription Factor ◽  
Matrix Metalloproteinase ◽  
Promoter Activity ◽  
Bovine Papillomavirus ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Matrix Metalloproteinase 1 ◽  
E6 And E7 ◽  
E7 Proteins

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type 1 (BPV-1) activity is necessary for the transformation phenotype of equine fibroblasts. Among the many changes induced by BPV-1, matrix metalloproteinase 1 (MMP-1) upregulation contributes to the invasiveness of equine fibroblasts. However, it is not yet known how BPV-1 proteins regulate equine MMP-1 expression. To elucidate this mechanism, the equine MMP-1 promoter was cloned and analysed. A putative activator protein-1 (AP-1)-binding site was demonstrated to be crucial for upregulated MMP-1 promoter activity by BPV-1. BPV-1 E6 and E7 proteins increased MMP-1 promoter activity, and inhibition of BPV-1 gene expression by small interfering RNA significantly reduced the promoter activity. c-Jun and Fra-1, two components of the AP-1 transcription factor complex, were overexpressed and activated by BPV-1 in equine fibroblasts. Finally, BPV-1 E5, E6 and E7 proteins increased MMP-1 mRNA and protein expression. In conclusion, the expression of MMP-1 can be enhanced by BPV-1 oncoproteins E6 and E7 through the AP-1 transcription factor and by E5 via an indirect mechanism. These findings shed light on the mechanism of BPV-1-mediated equine fibroblast infiltration and indicate that both BPV-1 oncoproteins and AP-1 could be potential targets for equine sarcoid therapy.

Apoptosis and proliferation ofperipheral blood T-cells as alternative processes in pathogenesis of diabetes mellitus type 1

2019 ◽  
Vol 1 (4) ◽  
pp. 16-20 ◽  
Author(s):  
A. V. Lugovaya ◽  
N. M. Kalinina ◽  
V. Ph. Mitreikin ◽  
Yu. P. Kovaltchuk ◽  
A. V. Artyomova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
High Risk ◽  
Peripheral Blood ◽  
Cellular Response ◽  
Proliferative Potential ◽  
Autoreactive T Cells ◽  
Alternative Processes

Apoptosis, along with proliferation, is a form of lymphocyte response to activating stimuli. In the early stages of cell differentiation, the apoptotic response prevails and it results to the formation of tolerance to inductor antigen. Mature lymphocytes proliferate in response to stimulation and it means the initial stage in the development of the immune response. Since in this case apoptosis and proliferation acts as alternative processes, their ratio can serve as a measure of the effectiveness of the cellular response to activating signals. The resistance of autoreactive T-cells to apoptosis is the main key point in the development of type 1 diabetes mellitus (T1DM). Autoreactive T-cells migrates from the bloodstream to the islet tissue of the pancreas and take an active part in b cells destruction. The resistance of autoreactive effector T-cells to apoptosis may suggest their high proliferative potential. Therefore, the comparative evaluation of apoptosis and proliferation of peripheral blood lymphocytes can give a more complete picture of their functional state and thus will help to reveal the causes of ineffective peripheral blood T-ceiis apoptosis in patients with T1DM and will help to understand more deeply the pathogenesis of the disease. in this article, the features of proliferative response of peripheral blood T-cells in patients with T1DM and in individuals with high risk of developing T1DM have been studied. Apoptosis of T-cell subpopulations has been investigated. The correlation between the apoptotic markers and the intensity of spontaneous and activation- induced in vitro T-cells proliferation of was revealed. it was determined, that autoreactive peripheral blood T-cells were resistant to apoptosis and demonstrated the increased proliferative potential in patients with T1DM and in individuals with high risk of developing T1DM.

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