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Pesquisa : D12.776.624.664.520.045 [Categoria DeCS]
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[PMID]:27651358
[Au] Autor:Sohn SY; Hearing P
[Ad] Endereço:Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York, USA.
[Ti] Título:Adenovirus Early Proteins and Host Sumoylation.
[So] Source:MBio;7(5), 2016 Sep 20.
[Is] ISSN:2150-7511
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human adenovirus genome is transported into the nucleus, where viral gene transcription, viral DNA replication, and virion assembly take place. Posttranslational modifications by small ubiquitin-like modifiers (SUMOs) are implicated in the regulation of diverse cellular processes, particularly nuclear events. It is not surprising, therefore, that adenovirus modulates and utilizes the host sumoylation system. Adenovirus early proteins play an important role in establishing optimal host environments for virus replication within infected cells by stimulating the cell cycle and counteracting host antiviral defenses. Here, we review findings on the mechanisms and functional consequences of the interplay between human adenovirus early proteins and the host sumoylation system.
[Mh] Termos MeSH primário: Proteínas Precoces de Adenovirus/metabolismo
Adenovírus Humanos/fisiologia
Interações Hospedeiro-Patógeno
Sumoilação
[Mh] Termos MeSH secundário: Proteínas Precoces de Adenovirus/genética
Adenovírus Humanos/genética
Núcleo Celular/virologia
Seres Humanos
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
Ubiquitina/metabolismo
Proteínas Virais/metabolismo
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (Small Ubiquitin-Related Modifier Proteins); 0 (Ubiquitin); 0 (Viral Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170721
[Lr] Data última revisão:
170721
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160922
[St] Status:MEDLINE


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[PMID]:22171254
[Au] Autor:Schmid M; Gonzalez RA; Dobner T
[Ad] Endereço:Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
[Ti] Título:CRM1-dependent transport supports cytoplasmic accumulation of adenoviral early transcripts.
[So] Source:J Virol;86(4):2282-92, 2012 Feb.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The life cycle of adenoviruses is divided by convention into early and late phases, separated by the onset of viral genome replication. Early events include virus adsorption, transport of the genome into the nucleus, and the expression of early genes. After the onset of viral DNA replication, transcription of the major late transcription unit (MLTU) and thereby synthesis of late proteins is induced. These steps are controlled by an orchestra of regulatory processes and require import of the genome and numerous viral proteins into the nucleus, as well as active transport of viral transcripts and proteins from the nucleus to the cytoplasm. The latter is achieved by exploiting the shuttling functions of cellular transport receptors, which normally stimulate the nuclear export of cellular mRNA and protein cargos. A set of adenoviral early and late proteins contains a leucine-rich nuclear export signal of the HIV-1 Rev type, known to be recognized by the cellular export receptor CRM1. However, a role for CRM1-dependent export in supporting adenoviral replication has not been established. To address this issue in detail, we investigated the impact of two different CRM1 inhibitors on several steps of the adenoviral life cycle. Inhibition of CRM1 led to a reduction in viral early and late gene expression, viral genome replication, and progeny virus production. For the first time, our findings indicate that CRM1-dependent shuttling is required for the efficient export of adenoviral early mRNA.
[Mh] Termos MeSH primário: Infecções por Adenoviridae/metabolismo
Proteínas Precoces de Adenovirus/genética
Adenovírus Humanos/metabolismo
Citoplasma/virologia
Carioferinas/metabolismo
RNA Viral/genética
Receptores Citoplasmáticos e Nucleares/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Infecções por Adenoviridae/genética
Infecções por Adenoviridae/virologia
Proteínas Precoces de Adenovirus/metabolismo
Adenovírus Humanos/genética
Transporte Biológico
Linhagem Celular
Núcleo Celular/genética
Núcleo Celular/metabolismo
Citoplasma/genética
Citoplasma/metabolismo
Regulação Viral da Expressão Gênica
Seres Humanos
Carioferinas/antagonistas & inibidores
Carioferinas/genética
RNA Viral/metabolismo
Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores
Receptores Citoplasmáticos e Nucleares/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (Karyopherins); 0 (RNA, Viral); 0 (Receptors, Cytoplasmic and Nuclear); 0 (exportin 1 protein)
[Em] Mês de entrada:1203
[Cu] Atualização por classe:150129
[Lr] Data última revisão:
150129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111216
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.06275-11


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[PMID]:21637763
[Au] Autor:Joshi A; Zhao B; Romanowski C; Rosen D; Flomenberg P
[Ad] Endereço:Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
[Ti] Título:Comparison of human memory CD8 T cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue.
[So] Source:PLoS One;6(5):e20068, 2011.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16-24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients.
[Mh] Termos MeSH primário: Proteínas Precoces de Adenovirus/sangue
Proteínas Precoces de Adenovirus/imunologia
Linfócitos T CD8-Positivos/imunologia
Proteínas do Capsídeo/sangue
Proteínas do Capsídeo/imunologia
Memória Imunológica/imunologia
Tonsila Palatina/metabolismo
[Mh] Termos MeSH secundário: Adulto
Biomarcadores
DNA Polimerase Dirigida por DNA/sangue
DNA Polimerase Dirigida por DNA/imunologia
Epitopos/imunologia
Seres Humanos
Cinética
Fenótipo
Linfócitos T Citotóxicos/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (Biomarkers); 0 (Capsid Proteins); 0 (Epitopes); 0 (hexon capsid protein, Adenovirus); EC 2.7.7.7 (DNA-Directed DNA Polymerase)
[Em] Mês de entrada:1109
[Cu] Atualização por classe:161025
[Lr] Data última revisão:
161025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110604
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0020068


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[PMID]:21454588
[Au] Autor:Fu J; Li L; Bouvier M
[Ad] Endereço:Department of Microbiology and Immunology, University of Illinois, College of Medicine, Chicago, Illinois 60612, USA.
[Ti] Título:Adenovirus E3-19K proteins of different serotypes and subgroups have similar, yet distinct, immunomodulatory functions toward major histocompatibility class I molecules.
[So] Source:J Biol Chem;286(20):17631-9, 2011 May 20.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our understanding of the mechanism by which the E3-19K protein from adenovirus (Ad) targets major histocompatibility complex (MHC) class I molecules for retention in the endoplasmic reticulum is derived largely from studies of Ad serotype 2 (subgroup C). It is not well understood to what extent observations on the Ad2 E3-19K/MHC I association can be generalized to E3-19K proteins of other serotypes and subgroups. The low levels of amino acid sequence homology between E3-19K proteins suggest that these proteins are likely to manifest distinct MHC I binding properties. This information is important as the E3-19K/MHC I interaction is thought to play a critical role in enabling Ads to cause persistent infections. Here, we characterized interaction between E3-19K proteins of serotypes 7 and 35 (subgroup B), 5 (subgroup C), 37 (subgroup D), and 4 (subgroup E) and a panel of HLA-A, -B, and -C molecules using native gel, surface plasmon resonance (SPR), and flow cytometry. Results show that all E3-19K proteins exhibited allele specificity toward HLA-A and -B molecules; this was less evident for Ad37 E3-19K. The allele specificity for HLA-A molecules was remarkably similar for different serotypes of subgroup B as well as subgroup C. Interestingly, all E3-19K proteins characterized also exhibited MHC I locus specificity. Importantly, we show that Lys(91) in the conserved region of Ad2 E3-19K targets the C terminus of the α2-helix (MHC residue 177) on MHC class I molecules. From our data, we propose a model of interaction between E3-19K and MHC class I molecules.
[Mh] Termos MeSH primário: Adenoviridae/imunologia
Proteínas E3 de Adenovirus/imunologia
Proteínas Precoces de Adenovirus/imunologia
Antígenos HLA-A/imunologia
Antígenos HLA-B/imunologia
[Mh] Termos MeSH secundário: Adenoviridae/genética
Adenoviridae/metabolismo
Proteínas E3 de Adenovirus/genética
Proteínas E3 de Adenovirus/metabolismo
Proteínas Precoces de Adenovirus/genética
Proteínas Precoces de Adenovirus/metabolismo
Linhagem Celular
Antígenos HLA-A/genética
Antígenos HLA-A/metabolismo
Antígenos HLA-B/genética
Antígenos HLA-B/metabolismo
Seres Humanos
Estrutura Secundária de Proteína
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adenovirus E3 Proteins); 0 (Adenovirus Early Proteins); 0 (HLA-A Antigens); 0 (HLA-B Antigens)
[Em] Mês de entrada:1107
[Cu] Atualização por classe:161202
[Lr] Data última revisão:
161202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110402
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M110.212050


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[PMID]:19112449
[Au] Autor:Kojaoghlanian T; Joseph A; Follenzi A; Zheng JH; Leiser M; Fleischer N; Horwitz MS; DiLorenzo TP; Goldstein H
[Ad] Endereço:Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
[Ti] Título:Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice.
[So] Source:Gene Ther;16(3):340-8, 2009 Mar.
[Is] ISSN:1476-5462
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with beta-cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted beta-cells from an alloimmune attack. The insulin-producing beta-cell line beta TC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RID alpha/beta. The efficiency of lentiviral transduction of beta TC-tet cells exceeded 85%. Lentivector expression of gp19K decreased surface class I major histocompatibility complex expression by over 90%, whereas RID alpha/beta expression inhibited cytokine-induced Fas upregulation by over 75%. beta TC-tet cells transduced with gp19K and RID alpha/beta lentivectors, but not with a control lentivector, provided prolonged correction of hyperglycemia after transplantation into diabetic BALB/c severe combined immunodeficient mice reconstituted with allogeneic immune effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering of beta-cells using gp19K- and RID alpha/beta-expressing lentiviral vectors may provide an alternative that has the potential to eliminate or reduce treatment with the potent immunosuppressive agents necessary at present for prolonged engraftment with transplanted islets.
[Mh] Termos MeSH primário: Diabetes Mellitus Experimental/terapia
Diabetes Mellitus Tipo 1/terapia
Engenharia Genética/métodos
Rejeição de Enxerto/prevenção & controle
Células Secretoras de Insulina/imunologia
Transplante das Ilhotas Pancreáticas/métodos
[Mh] Termos MeSH secundário: Proteínas E3 de Adenovirus/genética
Proteínas E3 de Adenovirus/imunologia
Proteínas Precoces de Adenovirus/genética
Proteínas Precoces de Adenovirus/imunologia
Animais
Diabetes Mellitus Experimental/imunologia
Diabetes Mellitus Tipo 1/imunologia
Modelos Animais de Doenças
Feminino
Vetores Genéticos
Rejeição de Enxerto/imunologia
Tolerância Imunológica
Lentivirus/genética
Camundongos
Camundongos Endogâmicos C3H
Camundongos Endogâmicos
Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
Transdução Genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adenovirus E3 Proteins); 0 (Adenovirus Early Proteins); 0 (E3 glycoprotein 19k, Adenovirus type 7)
[Em] Mês de entrada:1003
[Cu] Atualização por classe:161122
[Lr] Data última revisão:
161122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:081230
[St] Status:MEDLINE
[do] DOI:10.1038/gt.2008.172


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[PMID]:17401162
[Au] Autor:Groitl P; Dobner T
[Ad] Endereço:Institut fuer Medizinische Mikrobiologie und Hygiene, Universitaet Regensburg, Regensburg, Germany.
[Ti] Título:Construction of adenovirus type 5 early region 1 and 4 virus mutants.
[So] Source:Methods Mol Med;130:29-39, 2007.
[Is] ISSN:1543-1894
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This chapter describes a novel strategy that simplifies the generation and production of adenovirus type 5 (Ad5) mutants carrying defined mutations in early transcription units 1 (E1) and 4 (E4). The strategy involves three recombinant plasmids containing E1 (pE1-1235), E4 (pE4-1155), or the wild-type genome that lacks a portion of E3 (pH5pg4100). To generate recombinant viruses, mutations are first introduced into pE1- and/or pE4-transfer plasmids by site-directed mutagenesis. The mutagenized constructs are then ligated into plasmid pH5pg4100 containing the Ad backbone by direct cloning. Infectious viral DNAs are released from the recombinant plasmids by PacI-digestion and transfected into the complementing cell lines 293 or W162, and viral progeny are isolated and amplified. The advantages of this strategy are multiple: all cloning steps are carried out in Escherichia coli, and any genetic region of the viral E1 and/or E4 transcription units can be specifically modified or deleted. Moreover, foreign genes can be introduced into the E1 and/or E4 regions, and expression of viral or therapeutic genes can be controlled by cell-type specific and/or inducible promoters.
[Mh] Termos MeSH primário: Adenoviridae/genética
Proteínas Precoces de Adenovirus/genética
Mutação
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Clonagem Molecular
DNA Viral/genética
DNA Viral/isolamento & purificação
Escherichia coli/genética
Mutagênese Sítio-Dirigida
Plasmídeos
Mapeamento por Restrição
Transcrição Genética
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (DNA, Viral)
[Em] Mês de entrada:0708
[Cu] Atualização por classe:070402
[Lr] Data última revisão:
070402
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:070403
[St] Status:MEDLINE


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[PMID]:17166904
[Au] Autor:Nayak R; Pintel DJ
[Ad] Endereço:Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, 1201 E. Rollins Road, Columbia, MO 65211-7310, USA.
[Ti] Título:Positive and negative effects of adenovirus type 5 helper functions on adeno-associated virus type 5 (AAV5) protein accumulation govern AAV5 virus production.
[So] Source:J Virol;81(5):2205-12, 2007 Mar.
[Is] ISSN:0022-538X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Full replication of adeno-associated virus type 5 (AAV5) is sustained by adenovirus type 5 (Ad5) helper functions E1a, E1b, E2a, E4Orf6, and virus-associated (VA) RNA; however, their combined net enhancement of AAV5 replication was comprised of both positive and negative individual effects. Although Ad5 E4Orf6 was required for AAV5 genomic DNA replication, it also functioned together with E1b to degrade de novo-expressed, preassembled AAV5 capsid proteins and Rep52 in a proteosome-dependent manner. VA RNA enhanced accumulation of AAV5 protein, overcoming the degradative effects of E4Orf6, and was thus required to restore adequate amounts of AAV5 proteins necessary to achieve efficient virus production.
[Mh] Termos MeSH primário: Adenovírus Humanos/fisiologia
Dependovirus/fisiologia
Vírus Auxiliares/fisiologia
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Proteínas Precoces de Adenovirus/genética
Proteínas Precoces de Adenovirus/metabolismo
Adenovírus Humanos/genética
Proteínas do Capsídeo/genética
Proteínas do Capsídeo/metabolismo
Linhagem Celular
DNA Viral/biossíntese
DNA Viral/genética
Dependovirus/genética
Expressão Gênica
Genes Virais
Vírus Auxiliares/genética
Seres Humanos
RNA Viral/genética
Proteínas Virais/genética
Replicação Viral/genética
Replicação Viral/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (Capsid Proteins); 0 (DNA, Viral); 0 (RNA, Viral); 0 (Viral Proteins)
[Em] Mês de entrada:0703
[Cu] Atualização por classe:161208
[Lr] Data última revisão:
161208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:061215
[St] Status:MEDLINE


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[PMID]:17168793
[Au] Autor:Higashimoto Y; Yamagata Y; Itoh H
[Ad] Endereço:Department of Internal Medicine, Wakayama Medical University, Kihoku Hospital, 219 Myoji, Katsuragi-cho, Ito-gun, Wakayama Prefecture 649-7113, Japan. yhigashi@wakayama-med.ac.jp
[Ti] Título:Complex effect of adenovirus early region proteins on innate immune system.
[So] Source:Inflamm Allergy Drug Targets;5(4):229-37, 2006 Dec.
[Is] ISSN:1871-5281
[Cp] País de publicação:United Arab Emirates
[La] Idioma:eng
[Ab] Resumo:Adenoviruses (Ads) cause acute and persistent infections. The genome of Ads has five early transcription units that are the first viral genes expressed during an active infection. The Early Region 1A (E1A) gene of the adenovirus genome is crucial for adenovirus transformation of the host cell. Ads E1A block some aspects of the innate immune system to enable viruses to invade the host cell. E1A suppresses nitric oxide (NO) production through transcriptional control of the inducible NO synthase (iNOS) gene. This inhibition of NO production may enable the virus to persist in human tissue because NO is an antiviral effector of the innate immune system. E1A also blocks secretory leukoprotease inhibitor (SLPI) and elafin/skin-derived antileukoproteinase (SKALP) secretion by alveolar epithelial cells. Recent scientific evidence suggests that SLPI and elafin/SKALP have broad-spectrum antibiotic activities that include bactericidal and antifungal properties. The inhibition of inflammation by Ad early region proteins is complex, as certain early region proteins can promote as well as inhibit inflammation depending on the genetic context of the virus. E1A DNA and protein are frequently detected in the lungs of chronic obstructive pulmonary disease (COPD) patients and it is associated with an increased inflammatory response. E1A enhances intercellular adhesion molecule-1 and interleukin-8 mRNA expression with lipopolysaccharide stimulation. Understanding the roles of the Ad gene products in the induction and inhibition of innate inflammatory functions will help us to clarify the pathogenesis of the chronic respiratory illness including COPD.
[Mh] Termos MeSH primário: Infecções por Adenoviridae/fisiopatologia
Proteínas Precoces de Adenovirus/fisiologia
Imunidade Inata/fisiologia
[Mh] Termos MeSH secundário: Infecções por Adenoviridae/imunologia
Proteínas Precoces de Adenovirus/imunologia
Animais
Seres Humanos
Imunidade Inata/genética
Imunidade Inata/imunologia
Pneumonia/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adenovirus Early Proteins)
[Em] Mês de entrada:0701
[Cu] Atualização por classe:111110
[Lr] Data última revisão:
111110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:061216
[St] Status:MEDLINE


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[PMID]:16873238
[Au] Autor:Timpe JM; Verrill KC; Trempe JP
[Ad] Endereço:Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Ave., Toledo, OH 43614-5804, USA.
[Ti] Título:Effects of adeno-associated virus on adenovirus replication and gene expression during coinfection.
[So] Source:J Virol;80(16):7807-15, 2006 Aug.
[Is] ISSN:0022-538X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adeno-associated virus (AAV) is a nonpathogenic parvovirus that requires adenovirus (Ad) or another helper virus for a fully permissive infection. AAV-mediated inhibition of Ad is well documented, yet many details of this interaction remain unclear. In this study, we observed a maximum 50-fold decrease in infectious virus production and a 10- to 40-fold reduction in Ad DNA synthesis during coinfections with AAV. With the exception of the E3 gene, AAV decreased all steady-state Ad mRNA levels at 24 h postinfection (hpi) in a dose-dependent manner. However, not all transcription units were affected equally. E4 and late transcription were the most strongly inhibited, and E1A and E2A were the least affected. The temporal effects of AAV on Ad mRNA transcript levels also varied among the Ad genes. Ad protein expression paralleled mRNA levels at 24 hpi, suggesting that coinfecting AAV does not exert substantial effects on translation. In plasmid transfection assays, Rep78 protein most effectively limited Ad amplification, while Rep40 had no effect. Since E2a and E4 proteins are essential for efficient Ad DNA amplification, we examined the relationship between reduced E2A and E4 expression and decreased DNA amplification. Transfected Rep78 did not reduce E2A and E4 transcript levels prior to DNA replication. Also, AAV-induced inhibition of E2A and E4 mRNA production did not occur in the presence of hydroxyurea. It is therefore unlikely that decreased early gene expression is solely responsible for AAV's suppression of Ad DNA replication. Our results suggest that AAV amplification and/or Rep gene expression inhibits Ad DNA synthesis.
[Mh] Termos MeSH primário: Adenoviridae/genética
Proteínas Precoces de Adenovirus/genética
Dependovirus/fisiologia
Regulação Viral da Expressão Gênica
Replicação Viral
[Mh] Termos MeSH secundário: Células Cultivadas
DNA Helicases/genética
DNA Helicases/metabolismo
Replicação do DNA
DNA Viral/genética
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Dependovirus/efeitos dos fármacos
Amplificação de Genes
Expressão Gênica
Genes Virais/genética
Seres Humanos
Hidroxiureia/farmacologia
Biossíntese de Proteínas/genética
RNA Mensageiro/metabolismo
RNA Viral/metabolismo
Transcrição Genética
Proteínas Virais/genética
Proteínas Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (DNA, Viral); 0 (DNA-Binding Proteins); 0 (RNA, Messenger); 0 (RNA, Viral); 0 (Viral Proteins); 137750-19-7 (rep proteins, Adeno-associated virus 2); EC 3.6.4.- (DNA Helicases); EC 5.99.- (Rep40 protein, adeno-associated virus); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:0609
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060729
[St] Status:MEDLINE


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Fotocópia
[PMID]:16327990
[Au] Autor:Fernández-Soria V; Lleonart ME; Diaz-Fuertes M; Villuendas R; Sánchez-Prieto R; Fabra A; Ramón Y Cajal S
[Ad] Endereço:Department of Pathology, Hospital Vall d'Hebron, 08035 Barcelona, Spain.
[Ti] Título:Adenovirus E1A orchestrates the urokinase-plasminogen activator system and upregulates PAI-2 expression, supporting a tumor suppressor effect.
[So] Source:Int J Oncol;28(1):143-8, 2006 Jan.
[Is] ISSN:1019-6439
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Invasiveness and metastatic potential are the two most important properties defining malignancy. The adeno-virus E1A (Ad-E1A) gene has a dual effect as a proliferative gene and as a tumor-suppressor gene, decreasing tumor growth and the metastatic potential of malignant cells. In order to study genes related with the antimetastatic effect of Ad-E1A in human cells, we performed a microarray analysis using OncoChiptrade mark. In three independent experiments, NIH3T3, IMR90 and MDA MB 435 cells were infected with pLPC retroviruses carrying the adenovirus 12S E1A gene or the GFP gene. We analyzed cDNA expression by using the CNIO OncoChipTM, a cDNA microarray containing a total of 6386 genes represented by 7237 clones. uPA, uPAr, tPA, PAI-1 and PAI-2 were also studied at RNA and protein levels. Microarrays of cDNA expression, RT-PCR and Western blot performed in IMR90 E1A-expressing cells showed downregulation of uPA, uPAr, tPA, PAI-1 and upregulation of PAI-2. These results were confirmed in NIH3T3 and MDA MB 435 breast carcinoma cells, with PAI-2 upregulation by RT-PCR and Western blot. In addition, zymographic analysis demonstrated that E1A expression greatly reduced the gelatinase activity of the pro-MMP2 and -MMP9 proteins. We propose that adenovirus E1A may orchestrate the expression of most members of the urokinase-plasminogen activation system, downregulating potentially invasive genes and upregulating PAI-2, which is associated with a better prognosis in human tumors.
[Mh] Termos MeSH primário: Adenoviridae/genética
Proteínas Precoces de Adenovirus/fisiologia
Neoplasias da Mama/patologia
Carcinoma/patologia
Regulação Neoplásica da Expressão Gênica
Inibidor 1 de Ativador de Plasminogênio/biossíntese
[Mh] Termos MeSH secundário: Adenoviridae/fisiologia
Western Blotting
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Invasividade Neoplásica
Metástase Neoplásica
Análise de Sequência com Séries de Oligonucleotídeos
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Células Tumorais Cultivadas
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adenovirus Early Proteins); 0 (Plasminogen Activator Inhibitor 1); 0 (SERPINE1 protein, human)
[Em] Mês de entrada:0601
[Cu] Atualização por classe:061115
[Lr] Data última revisão:
061115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:051206
[St] Status:MEDLINE



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