The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Mauro Tognon - One of the best experts on this subject based on the ideXlab platform.
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specific antibodies reacting with sv40 large t antigen mimotopes in serum samples of healthy subjects
PLOS ONE, 2016Co-Authors: Mauro Tognon, Janet S. Butel, Silvia Pietrobon, Ilaria Bononi, Marco Manfrini, Alfredo Corallini, Angelo Taronna, Lorenzo Trevisiol, Emanuela Vaccher, Giuseppe BarbantibrodanoAbstract:Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA Tumor Virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18-65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses.
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Simian Virus 40 efficiently infects human T lymphocytes and extends their lifespan
Experimental hematology, 2012Co-Authors: Elisa Mazzoni, Cecilia Pancaldi, Stefania Maniero, Manola Comar, Fernanda Martini, Franca Nneka Alaribe, Gian Matteo Rigolin, Mauro TognonAbstract:The relevance of viral infections to the onset and progression of human hematologic malignancies and other blood diseases is still a matter of active investigation. Purified human T lymphocytes isolated from the peripheral blood mononuclear cells of healthy blood donors were experimentally infected with simian Virus 40 (SV40), a small DNA Tumor Virus. SV40-positive T lymphocytes extended their lifespan up to day 80 postinfection (PI). Expression of viral antigens, such as the large T antigen and the viral capsid protein VP1 from the early and late regions, respectively, was detected up to day 40 PI. SV40 viral progeny were continuously produced from day 10 to 40 PI. SV40 DNA sequences were detected in infected T cells for up to 80 days. Our data indicate that human T lymphocytes can be efficiently infected with SV40. Although T cells infected by SV40 were not immortalized, 30% of these lymphocytes appeared to be morphologically transformed with an enlarged T-cell shape. Our investigation provides a simple model for studying the interactions of human T lymphocytes with this small DNA Tumor Virus and it might represent an experimental tool for investigating new biomarkers and targets for innovative therapeutic approaches.
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Merkel cell polyomaVirus DNA sequences in the buffy coats of healthy blood donors
Blood, 2011Co-Authors: Cecilia Pancaldi, Valentina Corazzari, Stefania Maniero, Elisa Mazzoni, Manola Comar, Fernanda Martini, Mauro TognonAbstract:Merkel cell polyomaVirus (MCPyV), a DNA Tumor Virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in Tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy blood donors. This high seroprevalence suggests that MCPyV infection is widespread in humans. In our study, buffy coats, which were examined for MCPyV DNA Tag sequences, showed a prevalence of 22%. Viral DNA load was revealed in blood samples from 10 to 100 molecules/100 000 cells. DNA sequencing confirmed that polymerase chain reaction amplicons belong to the MCPyV strain, MKL-1. To interpret the putative role of MCPyV in chronic lymphocytic leukemia, we may infer that, during a long period of viral persistence in blood cells, this DNA Tumor Virus may generate mutants, which are able to participate as cofactors in the multistep process of cell transformation.
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Papilloma and polyoma DNA Tumor Virus sequences in female genital Tumors.
Cancer investigation, 2004Co-Authors: Fernanda Martini, Laura Iaccheri, Marcella Martinelli, Ruby Martinello, Grandi E, Gioacchino Mollica, Mauro TognonAbstract:Human papillomaViruses (HPVs) and BKV, JCV, and SV40 polyomaViruses (PYVs) are oncogenic Viruses associated with different human Tumors. Our aim was to determine if PYV and HPV sequences could be detected in human genital Tumors. HPV types 6b, 11, 16, and 18 and PYV were investigated in 22 genital Tumor samples and the corresponding adjacent normal tissues, by PCR and filter hybridization. HPV and PYV sequences were also searched in six sperm fluid and four peripheral blood cell (PBC) samples. HPV-16 sequences were revealed in 7 of 14 cervical Tumors and 1 of 1 vaginal adenocarcinoma, whereas 1 of 14 cervical carcinoma tested positive for HPV-18. Interestingly, each normal cervical tissue surrounding the neoplasm obtained from the same patient was positive for HPV type-16 and -18 with the same prevalence detected in Tumors. BKV sequences were found in 9 of 14 cervical Tumors, 1 of 7 vulvar Tumors, and 1 of 1 adenocarcinoma, but also in normal tissues from cervix (13 of 14), vulva (6 of 7), sperm fluid (5 ...
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c-fos Proto-Oncogene Transient Transcription Is Negatively Affected in the ELα4-2 Transformed Rat Cell Line
Pathobiology : journal of immunopathology molecular and cellular biology, 1993Co-Authors: Mauro Tognon, Maria Grazia Romanelli, Elisa Margherita Cattozzo, Chiara Bovolenta, Elio LiboiAbstract:To study the effects of the regulatory phosphoprotein ICP4 of the Herpes simplex Virus, (HSV), a DNA Tumor Virus, on the induction of gene expression by the epidermal growth factor (EGF), we have cons
Janet S. Butel - One of the best experts on this subject based on the ideXlab platform.
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SV40 and human mesothelioma.
Translational lung cancer research, 2020Co-Authors: Michele Carbone, Adi F. Gazdar, Janet S. ButelAbstract:Simian Virus 40 (SV40) is a DNA Tumor Virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey Virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.
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specific antibodies reacting with sv40 large t antigen mimotopes in serum samples of healthy subjects
PLOS ONE, 2016Co-Authors: Mauro Tognon, Janet S. Butel, Silvia Pietrobon, Ilaria Bononi, Marco Manfrini, Alfredo Corallini, Angelo Taronna, Lorenzo Trevisiol, Emanuela Vaccher, Giuseppe BarbantibrodanoAbstract:Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA Tumor Virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18-65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses.
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Association between SV40 and non-Hodgkin's lymphoma
Leukemia & Lymphoma, 2003Co-Authors: Janet S. Butel, Regis A. Vilchez, Jeffrey L. Jorgensen, Claudia A. KozinetzAbstract:Millions of people worldwide were inadvertently exposed to live simian Virus 40 (SV40) between 1955 and 1963 through immunization with SV40-contaminated polio vaccines. Although the prevalence of SV40 infections in humans is not known, numerous studies suggest that SV40 is a pathogen resident in the human population today. SV40 is a potent DNA Tumor Virus that is known to induce primary brain cancers, bone cancers, mesotheliomas, and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large Tumor antigen (T-ag), which inactivates the Tumor suppressor proteins p53 and pRb. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain and bone cancers and malignant mesotheliomas. Evidence suggests that there may be geographic differences in the frequency of these Virus-positive Tumors. Recent large independent controlled studies have shown that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). In our study, we analyzed systemic NHL from 76 HIV-1-positive and 78 HIV-1-negative patients, and nonmalignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without Tumors; 54 colon and breast carcinoma samples served as cancer controls. We used polymerase chain reaction (PCR) followed by Southern blot hybridization and DNA sequence analysis to detect DNAs of polyomaViruses and herpesViruses. SV40-specific DNA sequences were detected in 64 (42%) of 154 NHL, none of 186 nonmalignant lymphoid samples, and none of 54 control cancers. For NHL from HIV-1-positive patients, 33% contained SV40 DNA and 39% Epstein Barr Virus (EBV) DNA, whereas NHLs from HIV-1-negative patients were 50% positive for SV40 and 15% positive for EBV. Few Tumors were positive for both SV40 and EBV. Human herpesVirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B cell and follicular-type lymphomas. We conclude that SV40 is significantly associated with some types of NHL and that lymphomas should be added to the types of human cancers associated with SV40.
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cell and molecular biology of simian Virus 40 implications for human infections and disease
Journal of the National Cancer Institute, 1999Co-Authors: Janet S. Butel, John A LednickyAbstract:Simian Virus 40 (SV40), a polyomaVirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA Tumor Virus that induces Tumors in rodents and transforms many types of cells in culture, including those of human origin. This Virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of Virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human Tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the Virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.
Michele Carbone - One of the best experts on this subject based on the ideXlab platform.
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SV40 and human mesothelioma.
Translational lung cancer research, 2020Co-Authors: Michele Carbone, Adi F. Gazdar, Janet S. ButelAbstract:Simian Virus 40 (SV40) is a DNA Tumor Virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey Virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.
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the sv40 large t antigen p53 complexes bind and activate the insulin like growth factor i promoter stimulating cell growth
Cancer Research, 2008Co-Authors: Maurizio Bocchetta, Sandra Eliasz, Melissa A De Marco, Jennifer Rudzinski, Lei Zhang, Michele CarboneAbstract:Inactivation of cellular p53 is a crucial step in carcinogenesis. Accordingly, p53 is inactivated in most human cancers by different mechanisms. In cells infected with DNA Tumor Viruses, p53 is bound to the viral Tumor antigens (Tag). The current "dogma" views the Tag-p53 complexes as a way of sequestering and inactivating p53. Using primary human cells and SV40-transformed human cells, we show that in addition to inactivating p53 Tumor suppressor activities, the Tag-p53 complex has growth stimulatory activities that are required for malignant cell growth. We found that in human cells, Tag-p53 complexes regulate transcription of the insulin-like growth factor I (IGF-I) gene by binding to the IGF-I promoter together with pRb and p300. Depletion of p53 leads to structural rearrangements of this multiprotein complex, resulting in IGF-I promoter transcriptional repression and growth arrest. Our data provide a novel mechanistic and biological interpretation of the p53-Tag complexes and of DNA Tumor Virus transformation in general. In the model we propose, p53 is not a passive inactive partner of Tag. Instead the p53-Tag complex promotes malignant cell growth through its ability to activate the IGF-I signaling pathway.
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human mesotheliomas contain the simian Virus 40 regulatory region and large Tumor antigen DNA sequences
The Journal of Thoracic and Cardiovascular Surgery, 1998Co-Authors: Harvey I Pass, Jessica S Donington, Paola Rizzo, Michael Nishimura, Ronald C Kennedy, Michele CarboneAbstract:Abstract Background: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA Tumor Virus (simian Virus 40) has been shown to cause hamster mesotheliomas; we previously described simian Virus 40–like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian Virus 40 genome is present in mesotheliomas. Methods: Genomic DNA was extracted from snap frozen mesothelioma Tumor samples and from the simian Virus 40–induced hamster mesothelioma Tumor H9A. Polymerase chain reaction primers were used to amplify various simian Virus 40 large T-antigen regions including a 105–base pair amino terminus fragment, a 281–base pair carboxyl terminus fragment, and a 310–base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product. Results: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian Virus 40 regulatory sequences and Fok 1 digestion matched that of the hamster control Tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian Virus 40 strain 776. Conclusions: These data suggest an association between the simian Virus 40 Virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies. (J Thorac Cardiovasc Surg 1998;116:854-9)
David M Livingston - One of the best experts on this subject based on the ideXlab platform.
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Small DNA Tumor Viruses: Large Contributors to Biomedical Sciences
Virology, 2009Co-Authors: Peter M. Howley, David M LivingstonAbstract:Studies of the small DNA Tumor Viruses (the polyomaViruses, the adenoViruses and the papillomaViruses) have led to fundamental discoveries that have advanced our understanding of basic mammalian cell molecular biology processes such as transcription and DNA replication, uncovered pathways and genes often perturbed in human cancer, and identified bona fide human cancer Viruses. In this article we examine the many contributions that have come from the small DNA Tumor Virus field and provide a recounting of some of the major landmark discoveries.
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functional interactions of the retinoblastoma protein with mammalian d type cyclins
Cell, 1993Co-Authors: Mark E. Ewen, Hayla K Sluss, Junya Kato, Hitoshi Matsushime, Charles J Sherr, David M LivingstonAbstract:Abstract The retinoblastoma gene product (Rb) can interact efficiently with two of three D-type G 1 cyclins (D2 and D3) in vitro. Binding depended upon the minimal regions of Rb necessary for its growth-suppressive activity, as well as upon the D-type cyclin sequence motif shared with Rb-binding DNA Tumor Virus oncoproteins. Coexpression of the three D-type cyclins with the cyclin-dependent kinase (cdk4) in insect cells generated Rb kinase activity. By contrast, cyclins D2 and D3, but not D1, activated another such kinase, cdk2. Introduction of cyclin D2 and Rb into the Rb-deficient cell line SAOS-2 led to overt Rb hyperphosphorylation, whereas Rb, expressed alone or together with cyclin D1, remained unphosphorylated. Cyclin D2-dependent phosphorylation inhibited its binding to the transcription factor E2F and reversed the Rb G 1 exit block in the cell cycle. Thus, all D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known Tumor suppressor.
Robert F. Kalejta - One of the best experts on this subject based on the ideXlab platform.
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Human cytomegaloVirus pp71: A new viral tool to probe the mechanisms of cell cycle progression and oncogenesis controlled by the retinoblastoma family of Tumor suppressors
Journal of cellular biochemistry, 2004Co-Authors: Robert F. KalejtaAbstract:The DNA Tumor Virus oncogenes (adenoVirus E1A, simian Virus 40 (SV40) large T antigen, and papillomaVirus E7) have been instrumental in illuminating the molecules and mechanisms of cell cycle progression and carcinogenesis. However, since these multifunctional proteins target so many important cellular regulators, it is sometimes difficult to establish the functional importance of any individual interaction. Perhaps a herpesVirus protein, newly defined as a cell cycle regulator, can help address these issues. Like the DNA Tumor Virus proteins, the human cytomegaloVirus (HCMV) pp71 protein contains a retinoblastoma protein (Rb) binding motif (LxCxD), and stimulates DNA synthesis in quiescent cells. Unlike E1A, T antigen, and E7, pp71 expression does not induce apoptosis, nor does it cooperate to transform primary cells. Determining how pp71 induces cell cycle progression without invoking apoptosis or leading to cellular transformation may help in defining the signals that ultimately lead to these processes. © 2004 Wiley-Liss, Inc.
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human cytomegaloVirus pp71 stimulates cell cycle progression by inducing the proteasome dependent degradation of the retinoblastoma family of Tumor suppressors
Molecular and Cellular Biology, 2003Co-Authors: Robert F. Kalejta, Jill T Bechtel, Thomas ShenkAbstract:The oncoproteins of the DNA Tumor Viruses, adenoVirus E1A, simian Virus 40 T antigen, and papillomaVirus E7, each interact with the retinoblastoma family of Tumor suppressors, leading to cell cycle stimulation, apoptosis induction, and cellular transformation. These proteins utilize a conserved LXCXE motif, which is also found in cellular proteins, to target the retinoblastoma family. Here, we describe a herpesVirus protein that shares a subset of the properties of the DNA Tumor Virus oncoproteins but maintains important differences as well. The human cytomegaloVirus pp71 protein employs an LXCXD motif to attack the retinoblastoma family members and induce DNA synthesis in quiescent cells. pp71 binds to and induces the degradation of the hypophosphorylated forms of the retinoblastoma protein and its family members p107 and p130 in a proteasome-dependent manner. However, pp71 does not induce apoptosis and fails to transform cells. Thus, the similarities and differences in comparison to E1A, T antigen, and E7 make pp71 an interesting new tool with which to further dissect the role of the retinoblastoma/E2F pathway in cellular growth control and carcinogenesis.