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  1 / 3302 MEDLINE  
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[PMID]:29300759
[Au] Autor:Antoneli F; Passos FM; Lopes LR; Briones MRS
[Ad] Endereço:Laboratório de Genômica Evolutiva e Biocomplexidade, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo, UNIFESP, São Paulo, SP, Brazil.
[Ti] Título:A Kolmogorov-Smirnov test for the molecular clock based on Bayesian ensembles of phylogenies.
[So] Source:PLoS One;13(1):e0190826, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Divergence date estimates are central to understand evolutionary processes and depend, in the case of molecular phylogenies, on tests of molecular clocks. Here we propose two non-parametric tests of strict and relaxed molecular clocks built upon a framework that uses the empirical cumulative distribution (ECD) of branch lengths obtained from an ensemble of Bayesian trees and well known non-parametric (one-sample and two-sample) Kolmogorov-Smirnov (KS) goodness-of-fit test. In the strict clock case, the method consists in using the one-sample Kolmogorov-Smirnov (KS) test to directly test if the phylogeny is clock-like, in other words, if it follows a Poisson law. The ECD is computed from the discretized branch lengths and the parameter λ of the expected Poisson distribution is calculated as the average branch length over the ensemble of trees. To compensate for the auto-correlation in the ensemble of trees and pseudo-replication we take advantage of thinning and effective sample size, two features provided by Bayesian inference MCMC samplers. Finally, it is observed that tree topologies with very long or very short branches lead to Poisson mixtures and in this case we propose the use of the two-sample KS test with samples from two continuous branch length distributions, one obtained from an ensemble of clock-constrained trees and the other from an ensemble of unconstrained trees. Moreover, in this second form the test can also be applied to test for relaxed clock models. The use of a statistically equivalent ensemble of phylogenies to obtain the branch lengths ECD, instead of one consensus tree, yields considerable reduction of the effects of small sample size and provides a gain of power.
[Mh] Termos MeSH primário: Evolução Molecular
Modelos Genéticos
Filogenia
[Mh] Termos MeSH secundário: Animais
Ascomicetos/classificação
Ascomicetos/genética
Teorema de Bayes
Simulação por Computador
Ciclo-Oxigenase 1/genética
DNA/genética
Bases de Dados Genéticas
Produtos do Gene env/genética
Seres Humanos
Lentivirus/classificação
Lentivirus/genética
Distribuição de Poisson
Primatas/classificação
Primatas/genética
Proteínas/genética
Estatísticas não Paramétricas
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gene Products, env); 0 (Proteins); 9007-49-2 (DNA); EC 1.14.99.1 (Cyclooxygenase 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190826


  2 / 3302 MEDLINE  
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[PMID]:29300769
[Au] Autor:Schultz A; Germann A; Fuss M; Sarzotti-Kelsoe M; Ozaki DA; Montefiori DC; Zimmermann H; von Briesen H
[Ad] Endereço:Fraunhofer Institute for Biomedical Engineering IBMT, Joseph-von-Fraunhofer-Weg 1, Sulzbach, Germany.
[Ti] Título:Validation of an automated system for aliquoting of HIV-1 Env-pseudotyped virus stocks.
[So] Source:PLoS One;13(1):e0190669, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The standardized assessments of HIV-specific immune responses are of main interest in the preclinical and clinical stage of HIV-1 vaccine development. In this regard, HIV-1 Env-pseudotyped viruses play a central role for the evaluation of neutralizing antibody profiles and are produced according to Good Clinical Laboratory Practice- (GCLP-) compliant manual and automated procedures. To further improve and complete the automated production cycle an automated system for aliquoting HIV-1 pseudovirus stocks has been implemented. The automation platform consists of a modified Tecan-based system including a robot platform for handling racks containing 48 cryovials, a Decapper, a tubing pump and a safety device consisting of ultrasound sensors for online liquid level detection of each individual cryovial. With the aim to aliquot the HIV-1 pseudoviruses in an automated manner under GCLP-compliant conditions a validation plan was developed where the acceptance criteria-accuracy, precision as well as the specificity and robustness-were defined and summarized. By passing the validation experiments described in this article the automated system for aliquoting has been successfully validated. This allows the standardized and operator independent distribution of small-scale and bulk amounts of HIV-1 pseudovirus stocks with a precise and reproducible outcome to support upcoming clinical vaccine trials.
[Mh] Termos MeSH primário: Automação
Produtos do Gene env/metabolismo
HIV-1/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Gene Products, env)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190669


  3 / 3302 MEDLINE  
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[PMID]:28986292
[Au] Autor:Scicluna MT; Autorino GL; Nogarol C; Ricci I; Frontoso R; Rosone F; Nardini R
[Ad] Endereço:Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
[Ti] Título:Validation of an indirect ELISA employing a chimeric recombinant gag and env peptide for the serological diagnosis of equine infectious anemia.
[So] Source:J Virol Methods;251:111-117, 2018 Jan.
[Is] ISSN:1879-0984
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The National Reference Center for equine infectious anemia (EIA) validated a commercial ELISA (Eradikit EIAV Indirect ELISA, In3diagnostic , Turin, Italy) employing a chimeric recombinant gag and env peptide for the detection of EIA virus antibodies, following the guidelines of the World Organization for Animal Health. The validation parameters evaluated were: analytical sensitivity (Se) and specificity (Sp); diagnostic Se and Sp; precision, based on repeatability and reproducibility through the estimation of the standard deviation (SD) and the coefficient of variation (CV); accuracy, estimated from a multiple K and relative Sp and Se with respect to those of the agar gel immunodiffusion test (AGIDT). Positive and negative predictive values were also defined. The assay showed a high specificity and a limit of detection of 1.43 log major than AGIDT. Diagnostic Se was 100% and Sp was 99.3%, while SD values ranged from 1.58 to 5.01 with a CV between 2.8% and 28.8%. Multiple K was 0.98 and relative Se and Sp were respectively 99.1% and 100%. The assay proved to be robust and to possess a high sensitivity in detecting first antibodies produced at onset of infection as well as high analytic and diagnostic Se and Sp values, confirming it as a serological assay fit for purpose within EIA surveillance programs.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Antígenos Virais/imunologia
Ensaio de Imunoadsorção Enzimática/métodos
Anemia Infecciosa Equina/diagnóstico
Vírus da Anemia Infecciosa Equina/imunologia
Proteínas Recombinantes/imunologia
Testes Sorológicos/métodos
[Mh] Termos MeSH secundário: Animais
Antígenos Virais/genética
Produtos do Gene env/genética
Produtos do Gene env/imunologia
Produtos do Gene gag/genética
Produtos do Gene gag/imunologia
Cavalos
Valor Preditivo dos Testes
Proteínas Recombinantes/genética
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Gene Products, env); 0 (Gene Products, gag); 0 (Recombinant Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171008
[St] Status:MEDLINE


  4 / 3302 MEDLINE  
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[PMID]:29254991
[Au] Autor:Hernández JM; Podbilewicz B
[Ad] Endereço:Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany matias.hernandez@mpi-dortmund.mpg.de podbilew@technion.ac.il.
[Ti] Título:The hallmarks of cell-cell fusion.
[So] Source:Development;144(24):4481-4495, 2017 Dec 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cell-cell fusion is essential for fertilization and organ development. Dedicated proteins known as fusogens are responsible for mediating membrane fusion. However, until recently, these proteins either remained unidentified or were poorly understood at the mechanistic level. Here, we review how fusogens surmount multiple energy barriers to mediate cell-cell fusion. We describe how early preparatory steps bring membranes to a distance of ∼10 nm, while fusogens act in the final approach between membranes. The mechanical force exerted by cell fusogens and the accompanying lipidic rearrangements constitute the hallmarks of cell-cell fusion. Finally, we discuss the relationship between viral and eukaryotic fusogens, highlight a classification scheme regrouping a superfamily of fusogens called Fusexins, and propose new questions and avenues of enquiry.
[Mh] Termos MeSH primário: Adesão Celular/fisiologia
Fusão Celular
Fusão de Membrana/fisiologia
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans
Proteínas de Caenorhabditis elegans/metabolismo
Drosophila
Produtos do Gene env/metabolismo
Seres Humanos
Glicoproteínas de Membrana/metabolismo
Mioblastos/metabolismo
Proteínas da Gravidez/metabolismo
Proteínas SNARE/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (AFF-1 protein, C elegans); 0 (Caenorhabditis elegans Proteins); 0 (EFF-1 protein, C elegans); 0 (Gene Products, env); 0 (Membrane Glycoproteins); 0 (Pregnancy Proteins); 0 (SNARE Proteins); 0 (syncytin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.1242/dev.155523


  5 / 3302 MEDLINE  
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[PMID]:28726130
[Au] Autor:Zhang Z; Dai L; Jiang Y; Feng K; Liu L; Xia W; Yu F; Yao J; Xing W; Sun L; Zhang T; Wu H; Su B; Qiu M
[Ad] Endereço:National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
[Ti] Título:Transmission network characteristics based on env and gag sequences from MSM during acute HIV-1 infection in Beijing, China.
[So] Source:Arch Virol;162(11):3329-3338, 2017 Nov.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Molecular epidemiology can be used to identify human immunodeficiency virus (HIV) transmission clusters, usually using pol sequence for analysis. In the present study, we explored appropriate parameters to construct a simple network using HIV env and gag sequences instead of pol sequences for constructing a phylogenetic tree and a genetic transmission subnetwork, which were used to identify individuals with many potential transmission links and to explore the evolutionary dynamics of the virus among men who have sex with men (MSM) in Beijing. We investigated 70 acute HIV-1 infections, which consisted of HIV-1 subtype B (15.71%), the circulating recombinant forms CRF01_AE (47.14%), CRF07_BC (21.43%), CRF55_01B (1.43%), and CRF65_cpx (4.29%), and an unknown subtype (10.00%). By exploring the similarities and differences among HIV env, gag and pol sequences in describing the dynamics of the HIV-1 CRF01_AE transmission subnetwork among Beijing MSM, we found that four key points of the env sequences (strains E-2011_BJ.CY_16014, E-2011_BJ.FT_16017, E-2011_BJ.TZ_16064, and E-2011_BJ.XW_16035) contained more transmission information than gag sequences (three key points: strains G-2011_BJ.CY_16014, G-2011_BJ.FT_16017, and G-2011_BJ.XW_16035) and pol sequences (two key points: strains P-2011_BJ.CY_16014 and P-2011_BJ.XW_16035). Although the env and gag sequence results were similar to pol sequences in describing the dynamics of the HIV-1 CRF01_AE transmission subnetwork, we were able to obtain more precise information, allowing identification of key points of subnetwork expansion, based on HIV env and gag sequences instead of pol sequences. Taken together, the key points we found will improve our current understanding of how HIV spreads between MSM populations in Beijing and help to better target preventative interventions for promoting public health.
[Mh] Termos MeSH primário: Produtos do Gene env/metabolismo
Infecções por HIV/transmissão
Infecções por HIV/virologia
HIV-1/genética
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Adulto
Pequim/epidemiologia
Regulação Viral da Expressão Gênica
Produtos do Gene env/genética
Infecções por HIV/epidemiologia
Homossexualidade Masculina
Seres Humanos
Masculino
Filogenia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, env); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3485-z


  6 / 3302 MEDLINE  
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[PMID]:28651004
[Au] Autor:Lemaître C; Tsang J; Bireau C; Heidmann T; Dewannieux M
[Ad] Endereço:CNRS, UMR 9196, Institut Gustave Roussy, Villejuif, France.
[Ti] Título:A human endogenous retrovirus-derived gene that can contribute to oncogenesis by activating the ERK pathway and inducing migration and invasion.
[So] Source:PLoS Pathog;13(6):e1006451, 2017 Jun.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. Although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. Among these, the HERV-K(HML2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. Furthermore, they are induced in cancers, especially in melanoma, breast cancer and germ cell tumours, where viral particles, as well as the envelope protein (Env), can be detected. Here we show that HERV-K(HML2) Env per se has oncogenic properties. Its expression in a non-tumourigenic human breast epithelial cell line induces epithelial to mesenchymal transition (EMT), often associated with tumour aggressiveness and metastasis. In our model, this is typified by key modifications in a set of molecular markers, changes in cell morphology and enhanced cell motility. Remarkably, microarrays performed in 293T cells reveal that HERV-K(HML2) Env is a strong inducer of several transcription factors, namely ETV4, ETV5 and EGR1, which are downstream effectors of the MAPK ERK1/2 and are associated with cellular transformation. We demonstrate that HERV-K(HML2) Env effectively activates the ERK1/2 pathway in our experimental setting and that this activation depends on the Env cytoplasmic tail. In addition, this phenomenon is very specific, being absent with every other retroviral Env tested, except for Jaagsiekte Sheep Retrovirus (JSRV) Env, which is already known to have transforming properties in vivo. Though HERV-K Env is not directly transforming by itself, the newly discovered properties of this protein may contribute to oncogenesis.
[Mh] Termos MeSH primário: Retrovirus Endógenos/genética
Transição Epitelial-Mesenquimal/genética
Sistema de Sinalização das MAP Quinases/genética
[Mh] Termos MeSH secundário: Animais
Neoplasias da Mama/genética
Transformação Celular Neoplásica/genética
Produtos do Gene env/genética
Seres Humanos
Retrovirus Jaagsiekte de Ovinos
Invasividade Neoplásica
Ovinos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, env)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006451


  7 / 3302 MEDLINE  
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[PMID]:28388673
[Au] Autor:Hahn F; Schmalen A; Setz C; Friedrich M; Schlößer S; Kölle J; Spranger R; Rauch P; Fraedrich K; Reif T; Karius-Fischer J; Balasubramanyam A; Henklein P; Fossen T; Schubert U
[Ad] Endereço:Institute of Virology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
[Ti] Título:Proteolysis of mature HIV-1 p6 Gag protein by the insulin-degrading enzyme (IDE) regulates virus replication in an Env-dependent manner.
[So] Source:PLoS One;12(4):e0174254, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is a significantly higher risk for type II diabetes in HIV-1 carriers, albeit the molecular mechanism for this HIV-related pathology remains enigmatic. The 52 amino acid HIV-1 p6 Gag protein is synthesized as the C-terminal part of the Gag polyprotein Pr55. In this context, p6 promotes virus release by its two late (L-) domains, and facilitates the incorporation of the viral accessory protein Vpr. However, the function of p6 in its mature form, after proteolytic release from Gag, has not been investigated yet. We found that the mature p6 represents the first known viral substrate of the ubiquitously expressed cytosolic metalloendopeptidase insulin-degrading enzyme (IDE). IDE is sufficient and required for degradation of p6, and p6 is approximately 100-fold more efficiently degraded by IDE than its eponymous substrate insulin. This observation appears to be specific for HIV-1, as p6 proteins from HIV-2 and simian immunodeficiency virus, as well as the 51 amino acid p9 from equine infectious anaemia virus were insensitive to IDE degradation. The amount of virus-associated p6, as well as the efficiency of release and maturation of progeny viruses does not depend on the presence of IDE in the host cells, as it was shown by CRISPR/Cas9 edited IDE KO cells. However, HIV-1 mutants harboring IDE-insensitive p6 variants exhibit reduced virus replication capacity, a phenomenon that seems to depend on the presence of an X4-tropic Env. Furthermore, competing for IDE by exogenous insulin or inhibiting IDE by the highly specific inhibitor 6bK, also reduced virus replication. This effect could be specifically attributed to IDE since replication of HIV-1 variants coding for an IDE-insensitive p6 were inert towards IDE-inhibition. Our cumulative data support a model in which removal of p6 during viral entry is important for virus replication, at least in the case of X4 tropic HIV-1.
[Mh] Termos MeSH primário: Produtos do Gene env/metabolismo
HIV-1/fisiologia
Insulisina/metabolismo
Replicação Viral
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Células Cultivadas
Células HeLa
Seres Humanos
Insulina/metabolismo
Proteólise
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Gene Products, env); 0 (Insulin); 0 (gag Gene Products, Human Immunodeficiency Virus); 0 (p6 gag protein, Human immunodeficiency virus 1); EC 3.4.24.56 (Insulysin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174254


  8 / 3302 MEDLINE  
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[PMID]:28302141
[Au] Autor:Benesová M; Trejbalová K; Kovárová D; Vernerová Z; Hron T; Kucerová D; Hejnar J
[Ad] Endereço:Institute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic.
[Ti] Título:DNA hypomethylation and aberrant expression of the human endogenous retrovirus ERVWE1/syncytin-1 in seminomas.
[So] Source:Retrovirology;14(1):20, 2017 Mar 17.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Syncytin-1 and 2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. Previously, we have shown that the transcriptional suppression of ERVWE1 promoter is controlled epigenetically by DNA methylation and chromatin modifications. In this study, we describe the aberrant expression of syncytin-1 in biopsies of testicular germ cell tumors. RESULTS: We found efficient expression and splicing of syncytin-1 in seminomas and mixed germ cell tumors with seminoma component. Although another fusogenic gene, syncytin-2 was also derepressed in seminomas, its expression was significantly lower than that of syncytin-1. Neither the transcription factor GCM1 nor the increased copy number of ERVWE1 were sufficient for this aberrant expression of syncytin-1 in seminomas. In accordance with our recent finding of the highly increased expression of TET1 dioxygenase in most seminomas, the ERVWE1 promoter was significantly hypomethylated in comparison with the matched controls. In contrast, 5-hydroxymethylcytosine levels were not detectable at the ERVWE1 promoter. We further describe that another endogenous retroviral element adjacent to ERVWE1 remains transcriptionally suppressed and two additional HERV-W family members are only slightly upregulated in seminomas. CONCLUSIONS: We conclude that DNA demethylation of the ERVWE1 promoter in seminomas is a prerequisite for syncytin-1 derepression. We propose the spliced syncytin-1 expression as a marker of seminoma and suggest that aberrant expression of endogenous retroviruses might be a correlate of the hypomethylated genome of seminomas.
[Mh] Termos MeSH primário: DNA Viral/metabolismo
Retrovirus Endógenos/genética
Regulação da Expressão Gênica
Produtos do Gene env/biossíntese
Proteínas da Gravidez/biossíntese
Seminoma/patologia
Neoplasias Testiculares/patologia
[Mh] Termos MeSH secundário: Metilação de DNA
Epigênese Genética
Seres Humanos
Masculino
Seminoma/virologia
Neoplasias Testiculares/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Gene Products, env); 0 (Pregnancy Proteins); 0 (syncytin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170510
[Lr] Data última revisão:
170510
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-017-0342-9


  9 / 3302 MEDLINE  
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[PMID]:28292718
[Au] Autor:Boi S; Dis EV; Hansen EJ; Rosenke K; Peterson KE; Ferrell ME; Evans LH
[Ad] Endereço:Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840 United States.
[Ti] Título:Latent murine leukemia virus infection characterized by the release of non-infectious virions.
[So] Source:Virology;506:19-27, 2017 Jun.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clonal cell lines derived from cultures infected with a polytropic MuLV release vastly different levels of infectious virions ranging from undetectable to very high. Low producing clones release an overwhelming proportion of non-infectious virions containing retroviral RNA but deficient in the Env protein. Non-infectious virion production is not due to an inability of the cells to support infectious MuLV production or to an inherent replicative defectiveness of the proviruses. Reinfection of the lowest producing lines with the polytropic or an ecotropic MuLV results in enormous increases in the specific infectivity of the released virions. This indicates a reversible state of retroviral latency characterized by the release of non-infectious virions that is likely the result of insufficient levels of Env protein required for infectivity. The latency state described here may have important roles in in vivo retroviral infections including alterations of the immune response and the production of defective interfering particles.
[Mh] Termos MeSH primário: Vírus da Leucemia Murina/fisiologia
Infecções por Retroviridae/virologia
Vírion/fisiologia
Latência Viral
Liberação de Vírus
[Mh] Termos MeSH secundário: Animais
Produtos do Gene env/genética
Produtos do Gene env/metabolismo
Seres Humanos
Vírus da Leucemia Murina/genética
Camundongos
Vírion/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, env)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170705
[Lr] Data última revisão:
170705
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170316
[St] Status:MEDLINE


  10 / 3302 MEDLINE  
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[PMID]:28275184
[Au] Autor:Marno KM; O'Sullivan E; Jones CE; Díaz-Delfín J; Pardieu C; Sloan RD; McKnight Á
[Ad] Endereço:Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
[Ti] Título:RNA-Associated Early-Stage Antiviral Factor Is a Major Component of Lv2 Restriction.
[So] Source:J Virol;91(10), 2017 May 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication in human cells is restricted at early postentry steps by host inhibitory factors. We previously described and characterized an early-phase restriction of HIV-1 and -2 replication in human cell lines, primary macrophages, and peripheral blood mononuclear cells. The restriction was termed lentiviral restriction 2 (Lv2). The viral determinants of Lv2 susceptibility mapped to the HIV-2 envelope (Env) and capsid (CA). We subsequently reported a whole-genome small interfering RNA screening for factors involved in HIV that identified RNA-associated early-stage antiviral factor (REAF). Using HIV-2 chimeras of susceptible and nonsusceptible viruses, we show here that REAF is a major component of the previously described Lv2 restriction. Further studies of the viral CA demonstrate that the CA mutation I73V (previously called I207V), a potent determinant for HIV-2, is a weak determinant of susceptibility for HIV-1. More potent CA determinants for HIV-1 REAF restriction were identified at P38A, N74D, G89V, and G94D. These results firmly establish that in HIV-1, CA is a strong determinant of susceptibility to Lv2/REAF. Similar to HIV-2, HIV-1 Env can rescue sensitive CAs from restriction. We conclude that REAF is a major component of the previously described Lv2 restriction. Measures taken by the host cell to combat infection drive the evolution of pathogens to counteract or sidestep them. The study of such virus-host conflicts can point to possible weaknesses in the arsenal of viruses and may lead to the rational design of antiviral agents. Here we describe our discovery that the host restriction factor REAF fulfills the same criteria previously used to describe lentiviral restriction (Lv2). We show that, like the HIV-2 CA, the CA of HIV-1 is a strong determinant of Lv2/REAF susceptibility. We illustrate how HIV counteracts Lv2/REAF by using an envelope with alternative routes of entry into cells.
[Mh] Termos MeSH primário: Imunidade Inata
Proteínas/metabolismo
Replicação Viral
[Mh] Termos MeSH secundário: Animais
Proteínas do Capsídeo
Linhagem Celular
Produtos do Gene env/genética
Genoma Viral
HIV-1/genética
HIV-2/genética
Células HeLa
Interações Hospedeiro-Patógeno
Seres Humanos
Leucócitos Mononucleares/virologia
RNA Interferente Pequeno
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (Gene Products, env); 0 (Proteins); 0 (RNA, Small Interfering)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171028
[Lr] Data última revisão:
171028
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE



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