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[PMID]:28455653
[Au] Autor:Mazzoni E; Pietrobon S; Bilancia M; Vinante F; Rigo A; Ferrarini I; D'Agostino A; Casali MV; Martini F; Tognon M
[Ad] Endereço:Section of Pathology, Oncology and Experimental Biology, Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy.
[Ti] Título:High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin lymphoma.
[So] Source:Cancer Immunol Immunother;66(9):1189-1198, 2017 Sep.
[Is] ISSN:1432-0851
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new immunological investigation was carried out to study the association between non-Hodgkin lymphoma and Simian virus 40 (SV40). To this end, a new indirect ELISA was employed with two mimotopes from SV40 large T antigen (Tag), the viral oncoprotein, to analyse for specific reactions to antibodies in sera from non-Hodgkin lymphoma patients and controls, represented by healthy subjects (HS) and breast carcinoma (BC) patients. This study allowed us to assay a new sera collection from non-Hodgkin lymphoma patients (NHL, n = 254). To verify the association between NHL and SV40 Tag, two totally independent cohorts were analysed: NHL1 n = 150 and NHL2 n = 104. The epidemiological survey included sera from HS1, n = 150; HS2, n = 104 and BC, n = 78. This new indirect ELISA revealed that antibodies against SV40 Tag mimotopes are detectable in NHL1 and NHL2 sera with a prevalence of 37 and 36%, respectively. The prevalence of SV40-antibodies detected in both NHL1 and NHL2 cohorts differs statistically from controls, at 19% for HS1 (p < 0.01), HS2 (p < 0.05) and BC patients (p < 0.05). This study, carried out with an immunological assay with specific Tag oncoprotein mimotopes of Simian virus 40, reports the presence of IgG antibodies against the large Tumour antigen in non-Hodgkin lymphomas for the first time. Our immunological data with two independent NHL cohorts show a statistically significant association between Simian virus 40 Tag and non-Hodgkin lymphoma. These results suggest that SV40-positive non-Hodgkin lymphomas could be treated differently from those tested SV40-negative.
[Mh] Termos MeSH primário: Anticorpos Antivirais/imunologia
Antígenos Virais de Tumores/imunologia
Linfoma não Hodgkin/imunologia
Proteínas Oncogênicas/metabolismo
Vírus 40 dos Símios/imunologia
[Mh] Termos MeSH secundário: Adulto
Animais
Feminino
Seres Humanos
Linfoma não Hodgkin/patologia
Camundongos
Camundongos Transgênicos
Meia-Idade
Prevalência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Antigens, Viral, Tumor); 0 (Oncogene Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1007/s00262-017-2008-9


  2 / 2464 MEDLINE  
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[PMID]:29028833
[Au] Autor:Cheng J; Park DE; Berrios C; White EA; Arora R; Yoon R; Branigan T; Xiao T; Westerling T; Federation A; Zeid R; Strober B; Swanson SK; Florens L; Bradner JE; Brown M; Howley PM; Padi M; Washburn MP; DeCaprio JA
[Ad] Endereço:Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
[Ti] Título:Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.
[So] Source:PLoS Pathog;13(10):e1006668, 2017 Oct.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A) subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq) and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.
[Mh] Termos MeSH primário: Antígenos Virais de Tumores/metabolismo
Carcinoma de Célula de Merkel/virologia
Transformação Celular Viral/fisiologia
DNA Helicases/metabolismo
Proteínas de Ligação a DNA/metabolismo
Regulação Neoplásica da Expressão Gênica/fisiologia
Proteínas Proto-Oncogênicas c-myc/metabolismo
[Mh] Termos MeSH secundário: Antígenos Transformantes de Poliomavirus/metabolismo
Carcinoma de Célula de Merkel/genética
Carcinoma de Célula de Merkel/metabolismo
Linhagem Celular Tumoral
Seres Humanos
Immunoblotting
Imunoprecipitação
Poliomavírus das Células de Merkel
Infecções por Polyomavirus/complicações
Infecções por Polyomavirus/genética
Infecções por Polyomavirus/metabolismo
Infecções Tumorais por Vírus/complicações
Infecções Tumorais por Vírus/genética
Infecções Tumorais por Vírus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Polyomavirus Transforming); 0 (Antigens, Viral, Tumor); 0 (DNA-Binding Proteins); 0 (MYCL1 protein, human); 0 (Proto-Oncogene Proteins c-myc); EC 3.6.4.- (DNA Helicases); EC 3.6.4.12 (EP400 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006668


  3 / 2464 MEDLINE  
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[PMID]:28763479
[Au] Autor:Haymerle G; Janik S; Fochtmann A; Pammer J; Schachner H; Nemec L; Mildner M; Houben R; Grasl MC; Erovic BM
[Ad] Endereço:Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome.
[So] Source:PLoS One;12(8):e0180426, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to determine the prevalence of MCPyV in Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to evaluate possible prognostic factors. METHODS: Samples of MCC primaries and lymph node metastases were stained immunohistochemically for the MCPyV large T-antigen and expression was compared to patients´ clinical outcome. RESULTS: 41 MCC patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to 18 (82%) out of 22 lymph node metastases. Eleven patients with positive polyomavirus expression died from the carcinoma compared to 4 patients without virus expression. Cox regression analysis showed worse disease-free survival in patients with MCPyV compared to virus-negative lymph nodes (p = 0.002). CONCLUSIONS: To our knowledge this is the first study to describe a negative prognostic effect of the MCPyV expression in lymph node metastasis in MCC patients.
[Mh] Termos MeSH primário: Antígenos Virais de Tumores/metabolismo
Carcinoma de Célula de Merkel/patologia
Infecções por Polyomavirus/patologia
Neoplasias Cutâneas/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Carcinoma de Célula de Merkel/virologia
Intervalo Livre de Doença
Feminino
Regulação Neoplásica da Expressão Gênica
Regulação Viral da Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Metástase Linfática
Masculino
Poliomavírus das Células de Merkel/genética
Meia-Idade
Polyomavirus/genética
Prevalência
Prognóstico
Modelos de Riscos Proporcionais
Neoplasias Cutâneas/virologia
Resultado do Tratamento
Infecções Tumorais por Vírus/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180426


  4 / 2464 MEDLINE  
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[PMID]:28512245
[Au] Autor:Verhaegen ME; Mangelberger D; Harms PW; Eberl M; Wilbert DM; Meireles J; Bichakjian CK; Saunders TL; Wong SY; Dlugosz AA
[Ad] Endereço:Department of Dermatology, University of Michigan, Ann Arbor, Michigan.
[Ti] Título:Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.
[So] Source:Cancer Res;77(12):3151-3157, 2017 Jun 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. .
[Mh] Termos MeSH primário: Antígenos Virais de Tumores/metabolismo
Carcinoma de Célula de Merkel/virologia
Infecções por Polyomavirus/virologia
Neoplasias Cutâneas/virologia
Infecções Tumorais por Vírus/virologia
[Mh] Termos MeSH secundário: Animais
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
Carcinoma de Célula de Merkel/metabolismo
Modelos Animais de Doenças
Seres Humanos
Imuno-Histoquímica
Poliomavírus das Células de Merkel/imunologia
Camundongos
Camundongos Transgênicos
Reação em Cadeia da Polimerase
Infecções por Polyomavirus/metabolismo
Neoplasias Cutâneas/metabolismo
Infecções Tumorais por Vírus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATOH1 protein, human); 0 (Antigens, Viral, Tumor); 0 (Basic Helix-Loop-Helix Transcription Factors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-0035


  5 / 2464 MEDLINE  
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[PMID]:28430100
[Au] Autor:Carr M; Gonzalez G; Sasaki M; Ito K; Ishii A; Hang'ombe BM; Mweene AS; Orba Y; Sawa H
[Ad] Endereço:1​Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan 2​National Virus Reference Laboratory, University College Dublin, Belfield, Dublin 4, Ireland.
[Ti] Título:Discovery of African bat polyomaviruses and infrequent recombination in the large T antigen in the Polyomaviridae.
[So] Source:J Gen Virol;98(4):726-738, 2017 Apr.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bat species represent natural reservoirs for a number of high-consequence human pathogens. The present study investigated the diversity of polyomaviruses (PyVs) in Zambian insectivorous and fruit bat species. We describe the complete genomes from four newly proposed African bat PyV species employing the recently recommended criteria provided by the Polyomaviridae Study Group of the International Committee on Taxonomy of Viruses. A comprehensive phylogenetic and recombination analysis was performed to determine genetic relationships and the distribution of recombination events in PyV from mammalian and avian species. The novel species of PyV from Zambian bats segregated with members of the genera Alphapolyomavirus and Betapolyomavirus, forming monophyletic clades with bat and non-human primate PyVs. Miniopterus schreibersii polyomavirus 1 and 2 segregated in a clade with South American bat PyV species, Old World monkey and chimpanzee PyVs and Human polyomavirus 13 (New Jersey PyV). Interestingly, the newly described Egyptian fruit bat PyV, tentatively named Rousettus aegyptiacus polyomavirus 1, had the highest nucleotide sequence identity to species of PyV from Indonesian fruit bats, and Rhinolophus hildebrandtii polyomavirus 1 was most closely related to New World monkey PyVs. The distribution of recombination events in PyV genomes was non-random: recombination boundaries existed in the intergene region between VP1 and LTAg and also at the 3' end of VP2/3 in the structural genes, whereas infrequent recombination was present within the LTAg gene. These findings indicate that recombination within the LTAg gene has been negatively selected against during polyomaviral evolution and support the recent proposal for taxonomic classification based on LTAg to define novel PyV species.
[Mh] Termos MeSH primário: Antígenos Virais de Tumores/genética
Quirópteros/virologia
Infecções por Polyomavirus/veterinária
Polyomavirus/classificação
Polyomavirus/isolamento & purificação
Recombinação Genética
[Mh] Termos MeSH secundário: Animais
Análise por Conglomerados
Genoma Viral
Filogenia
Polyomavirus/genética
Infecções por Polyomavirus/virologia
Análise de Sequência de DNA
Homologia de Sequência
Zâmbia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000737


  6 / 2464 MEDLINE  
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[PMID]:28263390
[Au] Autor:Khan S; Oosterhuis K; Wunderlich K; Bunnik EM; Bhaggoe M; Boedhoe S; Karia S; Steenbergen RDM; Bosch L; Serroyen J; Janssen S; Schuitemaker H; Vellinga J; Scheper G; Zahn R; Custers J
[Ad] Endereço:Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.
[Ti] Título:Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease.
[So] Source:Int J Cancer;141(2):393-404, 2017 Jul 15.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High-risk Human papilloma virus (HPV) types are the causative agents of cervical cancer and several other anogenital malignancies. The viral proteins expressed in the (pre)malignant cells are considered ideal targets for immunological intervention. Many approaches have been evaluated for this purpose, mostly aiming at the induction of HPV16 E7- and/or E6-specific cellular immunogenicity. As clinical success has so far been limited, novel approaches are required. We describe the development and pre-clinical testing of a vaccine candidate consisting of replication-deficient adenovirus type 26 and 35 based vectors for the interception of HPV16- and HPV18-related disease. We developed HPV16- and HPV18-specific antigens consisting of fusion proteins of E2, E6 and E7. The vaccine will be suitable for every disease stage, from incident and persistent infections where E2 is predominantly expressed up to late stages where E6 and E7 expression are upregulated. Importantly E6 and E7 are present as reordered fragments to abrogate the transforming activity of these two proteins. Loss of transforming activity was demonstrated in different in vitro models. Robust T-cell immunogenicity was induced upon immunization of mice with the vaccine candidate. Finally, the developed vaccine vectors showed considerable therapeutic efficacy in the TC-1 mouse model. The absence of transforming activity of the antigens and the favorable immunogenicity profile of the adenovirus based vectors along with the fact that these vectors can be readily produced on a large scale makes this approach attractive for clinical evaluation.
[Mh] Termos MeSH primário: Dependovirus/fisiologia
Papillomavirus Humano 16/imunologia
Papillomavirus Humano 18/imunologia
Infecções por Papillomavirus/terapia
Neoplasias do Colo do Útero/terapia
[Mh] Termos MeSH secundário: Animais
Antígenos Virais de Tumores/imunologia
Feminino
Seres Humanos
Camundongos
Células NIH 3T3
Vacinas contra Papillomavirus/imunologia
Neoplasias do Colo do Útero/virologia
Replicação Viral
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor); 0 (Papillomavirus Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.30679


  7 / 2464 MEDLINE  
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[PMID]:28124141
[Au] Autor:Varsani A; Frankfurter G; Stainton D; Male MF; Kraberger S; Burns JM
[Ad] Endereço:The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, 85287-5001, USA. arvind.varsani@asu.edu.
[Ti] Título:Identification of a polyomavirus in Weddell seal (Leptonychotes weddellii) from the Ross Sea (Antarctica).
[So] Source:Arch Virol;162(5):1403-1407, 2017 May.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Viruses are ubiquitous in nature, however, very few have been identified that are associated with Antarctic animals. Here we report the identification of a polyomavirus in the kidney tissue of a deceased Weddell seal from the Ross Sea, Antarctica. The circular genome (5186 nt) has typical features of polyomaviruses with a small and larger T-antigen open reading frames (ORFs) and three ORFs encoding VP1, VP2 and VP3 capsid proteins. The genome of the Weddell seal polyomavirus (WsPyV) shares 85.4% genome-wide pairwise identity with a polyomavirus identified in a California sea lion. To our knowledge WsPyV is the first viral genome identified in Antarctic pinnipeds and the third polyomavirus to be identified from an Antarctic animal, the other two being from Adélie penguin (Pygoscelis adeliae) and a sharp-spined notothen (Trematomus pennellii), both sampled in the Ross sea. The GenBank accession number: KX533457.
[Mh] Termos MeSH primário: Antígenos Virais de Tumores/genética
Proteínas do Capsídeo/genética
Genoma Viral/genética
Polyomavirus/classificação
Polyomavirus/genética
Focas Verdadeiras/virologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Regiões Antárticas
Sequência de Bases
Feminino
Rim/virologia
Fases de Leitura Aberta/genética
Polyomavirus/isolamento & purificação
Alinhamento de Sequência
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor); 0 (Capsid Proteins)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3239-y


  8 / 2464 MEDLINE  
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[PMID]:28113048
[Au] Autor:Korup-Schulz SV; Lucke C; Moens U; Schmuck R; Ehlers B
[Ad] Endereço:1​Division 12 'Measles, Mumps, Rubella, and Viruses Affecting Immunocompromised Patients', Robert Koch Institute, Berlin, Germany.
[Ti] Título:Large T antigen variants of human polyomaviruses 9 and 12 and seroreactivity against their N terminus.
[So] Source:J Gen Virol;98(4):704-714, 2017 Apr.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The tumour antigens (TAgs) of mammalian polyomaviruses (PyVs) are key proteins responsible for modulating the host cell cycle and are involved in virus replication as well as cell transformation and tumour formation. Here we aimed to identify mRNA sequences of known and novel TAgs encoded by the recently discovered human polyomaviruses 9 and 12 (HPyV9 and HPyV12) in cell culture. Synthetic viral genomes were transfected into human and animal cell lines. Gene expression occurred in most cell lines, as measured by quantitative PCR of cDNA copies of mRNA encoding major structural protein VP1. Large TAg- and small TAg-encoding mRNAs were detected in all cell lines, and additional spliced mRNAs were identified encoding TAg variants of 145 aa (HPyV9) and 84 aa (HPyV12). Using as antigens in ELISA the N-terminal 78 aa common to all respective TAg variants of HPyV9 and HPyV12, seroreactivity of 100 healthy blood donors, 54 patients with malignant diseases of the gastrointestinal tract (GIT) and 32 patients with non-malignant diseases of the GIT was analysed. For comparison, the corresponding TAg N termini of BK PyV (BKPyV) and Merkel cell PyV (MCPyV) were included. Frequent reactivity against HPyV9, HPyV12 and BKPyV TAgs, but not MCPyV TAg, was observed in all tested groups. This indicates expression activity of the early region of three human PyVs in healthy and diseased subjects.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Antígenos Virais de Tumores/genética
Antígenos Virais de Tumores/imunologia
Variação Genética
Polyomavirus/genética
Polyomavirus/imunologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Ensaio de Imunoadsorção Enzimática
Seres Humanos
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Antigens, Viral, Tumor); 0 (RNA, Messenger)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000714


  9 / 2464 MEDLINE  
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[PMID]:28040372
[Au] Autor:Nguyen KD; Lee EE; Yue Y; Stork J; Pock L; North JP; Vandergriff T; Cockerell C; Hosler GA; Pastrana DV; Buck CB; Wang RC
[Ad] Endereço:Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas.
[Ti] Título:Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses.
[So] Source:J Am Acad Dermatol;76(5):932-940.e3, 2017 May.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Human polyomavirus (HPyV)6 and HPyV7 are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. OBJECTIVE: We determined whether biopsy specimens showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. METHODS: We screened biopsy specimens showing "peacock plumage" histology by polymerase chain reaction for HPyVs. Cases positive for HPyV6 or HPyV7 were then analyzed by immunohistochemistry, electron microscopy, immunofluorescence, quantitative polymerase chain reaction, and complete sequencing, including unbiased, next-generation sequencing. RESULTS: We identified 3 additional cases of HPyV6 or HPyV7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared with normal-appearing skin and the identification of intact virions by both electron microscopy and next-generation sequencing support a role for active viral infections in these skin diseases. LIMITATION: This was a small case series of archived materials. CONCLUSION: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a distinctive histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses."
[Mh] Termos MeSH primário: Ceratose/patologia
Ceratose/virologia
Infecções por Polyomavirus/complicações
Polyomavirus/isolamento & purificação
Prurido/patologia
Prurido/virologia
[Mh] Termos MeSH secundário: Adulto
Antígenos Virais de Tumores/análise
Biópsia
Proteínas do Capsídeo/análise
Estudos de Casos e Controles
Feminino
Seres Humanos
Queratinócitos/virologia
Masculino
Meia-Idade
Polyomavirus/genética
Polyomavirus/imunologia
Infecções por Polyomavirus/virologia
Estudos Retrospectivos
Pele/patologia
Pele/virologia
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor); 0 (Capsid Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170503
[Lr] Data última revisão:
170503
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170102
[St] Status:MEDLINE


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[PMID]:27795410
[Au] Autor:Takahashi K; Sekizuka T; Fukumoto H; Nakamichi K; Suzuki T; Sato Y; Hasegawa H; Kuroda M; Katano H
[Ad] Endereço:Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
[Ti] Título:Deep-Sequence Identification and Role in Virus Replication of a JC Virus Quasispecies in Patients with Progressive Multifocal Leukoencephalopathy.
[So] Source:J Virol;91(1), 2017 Jan 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:JC virus (JCV) is a DNA virus causing progressive multifocal leukoencephalopathy (PML) in immunodeficient patients. In the present study, 22 genetic quasispecies with more than 1.5% variant frequency were detected in JCV genomes from six clinical samples of PML by next-generation sequencing. A mutation from A to C at nucleotide (nt) 3495 in JCV Mad1 resulting in a V-to-G amino acid substitution at amino acid (aa) position 392 of the large T antigen (TAg) was identified in all six cases of PML at 3% to 19% variant frequencies. Transfection of JCV Mad1 DNA possessing the V392G substitution in TAg into IMR-32 and human embryonic kidney 293 (HEK293) cells resulted in dramatically decreased production of JCV-encoded proteins. The virus DNA copy number was also reduced in supernatants of the mutant virus-transfected cells. Transfection of the IMR-32 and HEK293 cells with a virus genome containing a revertant mutation recovered viral production and protein expression. Cotransfection with equal amounts of wild-type genome and mutated JCV genome did not reduce the expression of viral proteins or viral replication, suggesting that the mutation did not have any dominant-negative function. Finally, immunohistochemistry demonstrated that TAg was expressed in all six pathological samples in which the quasispecies were detected. In conclusion, the V392G amino acid substitution in TAg identified frequently in PML lesions has a function in suppressing JCV replication, but the frequency of the mutation was restricted and its role in PML lesions was limited. IMPORTANCE: DNA viruses generally have lower mutation frequency than RNA viruses, and the detection of quasispecies in JCV has rarely been reported. In the present study, a next-generation sequencer identified a JCV quasispecies with an amino acid substitution in the T antigen in patients with PML. In vitro studies showed that the mutation strongly repressed the expression of JC viral proteins and reduced the viral replication. However, because the frequency of the mutation was low in each case, the total expression of virus proteins was sustained in vivo. Thus, JC virus replicates in PML lesions in the presence of a mutant virus which is able to repress virus replication.
[Mh] Termos MeSH primário: DNA Viral/genética
Genoma Viral
Vírus JC/genética
Leucoencefalopatia Multifocal Progressiva/virologia
Mutação
Replicação Viral
[Mh] Termos MeSH secundário: Adulto
Idoso
Sequência de Aminoácidos
Substituição de Aminoácidos
Antígenos Virais de Tumores
Linhagem Celular Tumoral
Variações do Número de Cópias de DNA
DNA Viral/metabolismo
Feminino
Expressão Gênica
Células HEK293
Seres Humanos
Vírus JC/metabolismo
Leucoencefalopatia Multifocal Progressiva/patologia
Masculino
Meia-Idade
Neurônios/patologia
Neurônios/virologia
Alinhamento de Sequência
Análise de Sequência de DNA
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor); 0 (DNA, Viral)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE



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