Search

Your search keyword '"MESH: Polyomavirus"' showing total 7 results
Start Over Descriptor "MESH: Polyomavirus"
7 results on '"MESH: Polyomavirus"'

1. Emerging From the Unknown: Structural and Functional Features of Agnoprotein of Polyomaviruses

Author

Saribas, A Sami, Coric, Pascale, Hamazaspyan, Anahit, Davis, William, Axman, Rachel, White, Martyn, Abou-Gharbia, Magid, Childers, Wayne, Condra, Jon, Bouaziz, Serge, Safak, Mahmut, Saribas, A. Sami, Axman, Rachael, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Humans, viruses, MESH: Polyomavirus, MESH: Polyomavirus Infections, MESH: JC Virus, MESH: Animals, MESH: Transcription Factors, MESH: Viral Proteins, MESH: Viral Regulatory and Accessory Proteins
Abstract

International audience; Agnoprotein is an important regulatory protein of polyomaviruses, including JCV, BKV, and SV40. In the absence of its expression, these viruses are unable to sustain their productive life cycle. It is a highly basic phosphoprotein that localizes mostly to the perinuclear area of infected cells, although a small amount of the protein is also found in nucleus. Much has been learned about the structure and function of this important regulatory protein in recent years. It forms highly stable dimers/oligomers in vitro and in vivo through its Leu/Ile/Phe-rich domain. Structural NMR studies revealed that this domain adopts an alpha-helix conformation and plays a critical role in the stability of the protein. It associates with cellular proteins, including YB-1, p53, Ku70, FEZ1, HP1α, PP2A, AP-3, PCNA, and α-SNAP; and viral proteins, including small t antigen, large T antigen, HIV-1 Tat, and JCV VP1; and significantly contributes the viral transcription and replication. This review summarizes the recent advances in the structural and functional properties of this important regulatory protein. J. Cell. Physiol. 231: 2115-2127, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016
Full Text
View/download PDF

2. Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy

Author

Diotti, Ra, Mancini, Nicasio, Clementi, Nicola, Sautto, G, Moreno, Gj, Criscuolo, E, Cappelletti, F, Man, P, Forest, E, Remy, L, Giannecchini, S, Clementi, Massimo, Burioni, Roberto, Criscuolo, Elena, Dipartimento di Scienze della Vita, Seconda Universita di Napoli, Laboratoire RMN des Matériaux Nanoporeux (FRE3230), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Biotechnology, Fisica, Universita, INFN, Istituto Nazionale di Fisica Nucleare (INFN), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Diotti, Ra, Mancini, Nicasio, Clementi, Nicola, Sautto, G, Moreno, Gj, Criscuolo, E, Cappelletti, F, Man, P, Forest, E, Remy, L, Giannecchini, S, Clementi, Massimo, Burioni, Roberto, Criscuolo, Elena, and Thomas, Frank

Subjects
Neutralizing activity, MESH: Polyomavirus, JC virus, medicine.disease_cause, Antibodies, Viral, Epitope, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, Epitopes, Natalizumab, Demyelinating disease, Cloning, Molecular, MESH: Capsid Proteins, Progressive multifocal leukoencephalopathy (PML), [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Progressive multifocal leukoencephalopathy, MESH: Neutralization Tests, Leukoencephalopathy, Progressive Multifocal, Antibodies, Monoclonal, JCPyV, 3. Good health, Antibody, Polyomavirus, medicine.drug, Monoclonal antibody, JCPyV, Monoclonal antibody, Multiple sclerosis, Natalizumab, Neutralizing activity, Progressive multifocal leukoencephalopathy (PML) [KEYWORDS], MESH: Epitopes, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], medicine.drug_class, Biology, Antibodies, Monoclonal, Humanized, Multiple sclerosis, Neutralization Tests, Virology, medicine, Humans, MESH: Cloning, Molecular, Pharmacology, MESH: Humans, MESH: Leukoencephalopathy, Progressive Multifocal, MESH: Multiple Sclerosis, medicine.disease, Antibodies, Neutralizing, MESH: Antibodies, Monoclonal, Humanized, Immunology, biology.protein, Capsid Proteins, MESH: Antibodies, Viral
Abstract

JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment.Copyright © 2014 Elsevier B.V. All rights reserved.

Published
2014

3. Merkel Cell Polyomavirus Strains in Patients with Merkel Cell Carcinoma

Author

Pierre Coursaget, Christine Clavel, Emmanuelle Le Bidre, Julien Gaitan, Antoine Touzé, Gérard Lorette, Anne Durlach, François Aubin, Angélique Doussinaud, Annabel Maruani, Serge Guyétant, Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 ( PERPMP ), Université de Reims Champagne-Ardenne ( URCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -CHU de Reims - Hôpital Maison Blanche, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Sequence Analysis, DNA, Pathology, Skin Neoplasms, MESH : Molecular Sequence Data, Epidemiology, MESH: Polyomavirus, MESH : Aged, MESH : Capsid Proteins, lcsh:Medicine, Merkel cell polyomavirus, Polymerase Chain Reaction, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Aged, 80 and over, 0302 clinical medicine, MESH : Female, MESH : DNA, Viral, MESH : Carcinoma, Merkel Cell, Dna viral, MESH : Polymerase Chain Reaction, MESH: Capsid Proteins, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, integumentary system, biology, Merkel cell carcinoma, Dispatch, virus diseases, food and beverages, Middle Aged, MESH : Polyomavirus, 3. Good health, Neuroendocrine Carcinomas, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, France, MESH : Merkel Cells, Merkel cell, Microbiology (medical), medicine.medical_specialty, virus transforming agent, MESH : Male, Molecular Sequence Data, MESH: Polyomavirus Infections, polyomavirus, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, medicine, Carcinoma, Humans, lcsh:RC109-216, viruses, MESH : Middle Aged, In patient, MESH : Aged, 80 and over, MESH : France, Aged, 030304 developmental biology, Polyomavirus Infections, MESH: Molecular Sequence Data, MESH: Humans, MESH: Skin Neoplasms, lcsh:R, MESH : Skin Neoplasms, MESH : Humans, MESH: Tumor Virus Infections, MESH: Polymerase Chain Reaction, MESH: Carcinoma, Merkel Cell, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Merkel cells, MESH: Male, MESH : Polyomavirus Infections, MESH: DNA, Viral, Carcinoma, Merkel Cell, MESH: France, Tumor Virus Infections, MESH: Merkel Cells, DNA, Viral, Capsid Proteins, MESH : Tumor Virus Infections, MESH: Female, MESH : Sequence Analysis, DNA
Abstract

International audience; We investigated whether Merkel cell carcinoma (MCC) patients in France carry Merkel cell polyomavirus (MCPyV) and then identified strain variations. All frozen MCC specimens and 45% of formalin-fixed and paraffin-embedded specimens, but none of the non-MCC neuroendocrine carcinomas specimens, had MCPyV. Strains from France and the United States were similar.

Published
2009
Full Text
View/download PDF

4. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome

Author

Gérard Lorette, Eve Maubec, Agnès Carlotti, Annabel Maruani, Marie-Françoise Avril, Maxime Fleury, Raphaël Cazal, Serge Guyétant, Mauro Tognon, Flore Rozenberg, Françoise Arnold, Antoine Touzé, Emmanuelle Le Bidre, François Aubin, Pierre Coursaget, Hélène Laude, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie, Hôpital Saint-Vincent de Paul, Laboratoire Analyse, Géométrie et Applications ( LAGA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut Galilée-Centre National de la Recherche Scientifique ( CNRS ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de Dermatologie, Hôpital Cochin, AP-HP, Paris, Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]

Subjects
Pathology, MESH: Chi-Square Distribution, MESH: Lymphatic Metastasis, MESH: Polyomavirus, MESH : Aged, MESH : Prospective Studies, MESH: Risk Assessment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Merkel cell carcinoma, 0302 clinical medicine, MESH: Up-Regulation, MESH : Neoplasm Staging, MESH : Up-Regulation, MESH: Capsid Proteins, 0303 health sciences, MESH: Middle Aged, Antibody titer, food and beverages, MESH : Lymphatic Metastasis, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Case-Control Studies, MESH : Polyomavirus, 3. Good health, Oncology, 030220 oncology & carcinogenesis, MESH: RNA, Viral, VIRUS, Antibody, MESH : Case-Control Studies, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Aged, 80 and over, MESH: Kaplan-Meier Estimate, MESH: Humans, MESH : Chi-Square Distribution, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, medicine.disease, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, MESH: Female, SKIN, MESH: Antibodies, Viral, Cancer Research, MESH : Capsid Proteins, Merkel cell polyomavirus, Human skin, antibody, immune system, outcome, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, MESH: Risk Factors, MESH : Tumor Markers, Biological, INFECTION, EPIDEMIOLOGY, MESH : Female, MESH : Risk Assessment, MESH : Carcinoma, Merkel Cell, MESH: Aged, MESH : Prognosis, biology, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Neoplasm Staging, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, ETIOLOGY, MESH : Disease-Free Survival, MESH : Time Factors, circulatory and respiratory physiology, MESH : Antibodies, Viral, EXPRESSION, TISSUES, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Kaplan-Meier Estimate, medicine, MESH : RNA, Viral, MESH : France, 030304 developmental biology, Insect cell, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH: Time Factors, Cancer, MESH: Carcinoma, Merkel Cell, biology.organism_classification, MESH: Male, MESH: Prospective Studies, MESH: France, Geometric mean titer, MCV, biology.protein, business
Abstract

Purpose A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics. Patients and Methods Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells. Results Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002). Conclusion High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.

Published
2011
Full Text
View/download PDF

5. [Merkel cell carcinoma: a virus-induced tumor?]

Author

Maruani , Anabel, Lebidre , Emmanuelle, Touzé , Antoine, Aubin , François, Guyétant , Serge, Lorette , Gérard, Coursaget , Pierre, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Polyomavirus Infections, MESH: Humans, Skin Neoplasms, MESH: Polyomavirus, MESH: Skin Neoplasms, MESH: Polyomavirus Infections, MESH : Humans, MESH : Skin Neoplasms, MESH: Tumor Virus Infections, MESH: Carcinoma, Merkel Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Polyomavirus, MESH : Polyomavirus Infections, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Carcinoma, Merkel Cell, Tumor Virus Infections, Humans, MESH : Carcinoma, Merkel Cell, Polyomavirus, MESH : Tumor Virus Infections, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008
Full Text
View/download PDF

6. Mutations within the hamster polyomavirus large T antigen domain involved in pRb binding impair virus productive cycle and immortalization capacity

Author

Goutebroze, L., La Roche Saint Andre, C., Scherneck, S., Jean Feunteun, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
MESH: Rats, MESH: Polyomavirus, MESH: Mesocricetus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Antigens, Polyomavirus Transforming, Molecular Sequence Data, MESH: Cricetinae, MESH: Amino Acid Sequence, MESH: Base Sequence, Virus Replication, Retinoblastoma Protein, Structure-Activity Relationship, MESH: Structure-Activity Relationship, Cricetinae, MESH: Protein Binding, Animals, Point Mutation, MESH: Animals, Amino Acid Sequence, MESH: Point Mutation, MESH: Molecular Sequence Data, MESH: Antigens, Polyomavirus Transforming, Base Sequence, Mesocricetus, MESH: Virus Replication, MESH: Retinoblastoma Protein, Cell Transformation, Viral, Rats, Cell Transformation, Neoplastic, MESH: Cell Transformation, Neoplastic, MESH: Cell Transformation, Viral, Polyomavirus, Protein Binding
Abstract

International audience; Hamster polyomavirus (HaPV) causes lymphoma and leukemia when injected into newborn Syrian hamsters and achieves full transformation of rodent fibroblasts in vitro. It offers a comprehensive model to study at a molecular level the contributions of the viral oncogenes to neoplastic transformation in vitro and in the animal. We have investigated the ability of HaPV large T antigen to form a complex with the product of the retinoblastoma gene (pRb) in vitro. In this report, we demonstrate that HaPV large T antigen can indeed complex the pRb polypeptide. In order to investigate to what extent this interaction might contribute to tumor induction by the virus, we have introduced two different point mutations within the putative pRb-binding sequence of large T antigen, and as a preliminary to in vivo experiments we have studied their effects in vitro on some biological activities relevant to tumor induction. We show that the substitution (Glu-134-->Lys) obliterates pRb binding, suggesting that Glu-134 participates in the interaction between pRb and large T antigen, whereas the substitution (Glu-135-->Lys) has no effect. The Lys-134 mutation is strongly deleterious to the immortalization capacity of the viral genome, whereas the Lys-135 mutation has no effect. Neither of the two mutations affects the capacity of the viral genome to induce foci formation in the rat established cell line F111. These results indicate that the interaction between large T and pRb is required in the immortalization process but irrelevant to transformation. Both mutants show at least partial impairment of replication and productive cycle.

7. Early gene expression in lymphoma-associated hamster polyomavirus viral genomes

Author

veronique Delmas, La Roche Saint André, C., Gardes, M., Laurence Goutebroze, Feunteun, J., Institut du Fer à Moulin (IFM - Inserm U1270 - SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Gene Expression Regulation, Viral, Genes, Viral, Lymphoma, Transcription, Genetic, MESH: Polyomavirus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Molecular Sequence Data, MESH: Cricetinae, MESH: Viral Structural Proteins, MESH: Base Sequence, Virus Replication, Polymerase Chain Reaction, MESH: Gene Expression Regulation, Viral, Cricetinae, MESH: Promoter Regions, Genetic, Animals, MESH: Animals, MESH: Hydrogen Bonding, Promoter Regions, Genetic, Viral Structural Proteins, MESH: Genes, Viral, MESH: Molecular Sequence Data, Base Sequence, MESH: Transcription, Genetic, MESH: Virus Replication, MESH: Polymerase Chain Reaction, Hydrogen Bonding, MESH: DNA, Viral, Oligodeoxyribonucleotides, MESH: RNA, Viral, DNA, Viral, MESH: Oligodeoxyribonucleotides, RNA, Viral, MESH: Lymphoma, Polyomavirus
Abstract

International audience; Hamster polyomavirus (HaPV) is the causal agent of hair follicle epithelioma in hamsters belonging to a colony bred in Berlin-Buch. These tumors shed virus particles that are assembled in the keratinized layer of the epidermis. By contrast, HaPV induces lymphomas after inoculation into newborn hamsters from a distinct colony bred in Potsdam. These lymphoid tumors accumulate massive amounts of episomal viral genomes characterized by deletions that alter specifically the regulatory and the late coding sequences. Assuming that these alterations of the regulatory region may affect the transcription of the viral oncogenes in the tumor cells, the transcriptional activity of the wild-type and deleted early promoters have been studied in vitro in transient chloramphenicol acetyltransferase (CAT) expression assays. These assays performed in various cell types demonstrate that both versions of the HaPV early promoter carry a weak constitutive activity. Simultaneous expression of the HaPV early gene products leads to a strong stimulation of CAT activity with a concomitant activation of the replication of the plasmid constructs. The results obtained with origin-defective CAT vectors indicate that the replication contributes significantly to the stimulating effect of the early gene products. Indeed, transfection of massive amounts of CAT vectors that are unable to replicate can simulate the dosage effect of replication and also leads to measurable CAT activities. Under these conditions, the wild-type promoter is more active than the deleted version, indicating that sequences within the deletion carry a distinct stimulatory effect on transcription. This conclusion is supported by the observation that the lymphoma cells contain a low level of early transcripts, indicating that the deleted episomal viral templates accumulated in these tumors carry a weak transcriptional activity.

Catalog

Books, media, physical & digital resources
See catalog results