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  1 / 12579 MEDLINE  
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[PMID]:29408624
[Au] Autor:Wang X; Li W; Xu X; Wang W; He K; Fan H
[Ad] Endereço:Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China; College of Veterinary Medicine, Nanjing
[Ti] Título:Phylogenetic analysis of two goat-origin PCV2 isolates in China.
[So] Source:Gene;651:57-61, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Complete genome characterization of non-porcine origin Porcine circovirus type 2 (PCV2) was first described in 2014 in China. In the present study, we first identified PCV2 nucleotides in goat samples and the prevalence of PCV2 in goat was 6.15%. However, only two new strains, Goat2014-4 and Goat2014-5, could be completely sequenced. The genome of the strain Goat2014-4, which collected from the goat infected with PPRV, contains 1766 nt; strain Goat2014-5, which originated from a healthy goat, is comprised of 1767 nt. The results showed that they shared the highest nucleotide identity with BDH and the lowest similarity with DK1980PMWSfree strain and they belonged only to genotype PCV2d. Meanwhile, they shared higher homology with porcine-origin PCV2 strains than others. Moreover, a detailed analysis of the capsid amino acid sequences revealed that there were distinct differences for goat2014-4 (708 bp) and goat2014-5 (705 bp); strain Goat2014-4 showed an elongation of two amino acids, and strains Goat2014-5 showed an elongation of one amino acid compared with other reference strains. This is the first report of the genetic analysis of goat-origin PCV2 isolates. It also provides an additional supported evidence for cross-species transmission of PCV2.
[Mh] Termos MeSH primário: Infecções por Circoviridae/veterinária
Circovirus/classificação
Circovirus/isolamento & purificação
Doenças das Cabras/virologia
[Mh] Termos MeSH secundário: Animais
Proteínas do Capsídeo/genética
China
Infecções por Circoviridae/virologia
Frequência do Gene
Genoma Viral
Cabras
Filogenia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


  2 / 12579 MEDLINE  
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[PMID]:28453853
[Au] Autor:Seppälä H; Virtanen E; Saarela M; Laine P; Paulín L; Mannonen L; Auvinen P; Auvinen E
[Ad] Endereço:Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
[Ti] Título:Single-Molecule Sequencing Revealing the Presence of Distinct JC Polyomavirus Populations in Patients With Progressive Multifocal Leukoencephalopathy.
[So] Source:J Infect Dis;215(6):889-895, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by reactivation of JC polyomavirus (JCPyV) in immunosuppressed individuals and lytic infection by neurotropic JCPyV in glial cells. The exact content of neurotropic mutations within individual JCPyV strains has not been studied to our knowledge. Methods: We exploited the capacity of single-molecule real-time sequencing technology to determine the sequence of complete JCPyV genomes in single reads. The method was used to precisely characterize individual neurotropic JCPyV strains of 3 patients with PML without the bias caused by assembly of short sequence reads. Results: In the cerebrospinal fluid sample of a 73-year-old woman with rapid PML onset, 3 distinct JCPyV populations could be identified. All viral populations were characterized by rearrangements within the noncoding regulatory region (NCCR) and 1 point mutation, S267L in the VP1 gene, suggestive of neurotropic strains. One patient with PML had a single neurotropic strain with rearranged NCCR, and 1 patient had a single strain with small NCCR alterations. Conclusions: We report here, for the first time, full characterization of individual neurotropic JCPyV strains in the cerebrospinal fluid of patients with PML. It remains to be established whether PML pathogenesis is driven by one or several neurotropic strains in an individual.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/genética
Líquido Cefalorraquidiano/virologia
Vírus JC/isolamento & purificação
Leucoencefalopatia Multifocal Progressiva/virologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Feminino
Finlândia
Genoma
Seres Humanos
Vírus JC/genética
Masculino
Meia-Idade
Mutação
Reação em Cadeia da Polimerase
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (VP1 protein, polyomavirus)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jiw399


  3 / 12579 MEDLINE  
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[PMID]:28942015
[Au] Autor:Chen P; Wang H; Tao Z; Xu A; Lin X; Zhou N; Wang P; Wang Q
[Ad] Endereço:Department of Epidemiology, School of Public Health, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, People's Republic of China.
[Ti] Título:Multiple transmission chains of coxsackievirus A4 co-circulating in China and neighboring countries in recent years: Phylogenetic and spatiotemporal analyses based on virological surveillance.
[So] Source:Mol Phylogenet Evol;118:23-31, 2018 Jan.
[Is] ISSN:1095-9513
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Coxsackievirus A4 (CV-A4) has been reported frequently in association with many infectious diseases and cases of hand, foot, and mouth disease potentially associated with CV-A4 infection are also identified. This study summarized the Shandong CV-A4 strains isolated from 25years acute flaccid paralysis surveillance, with an emphasis on exploring the phylogenetic analyses and spatiotemporal dynamics of CV-A4 at the global scale. We sampled 43 CV-A4 isolates and utilized VP1 gene to construct phylogenetic trees. Further extensive Bayesian phylogeographic analysis was carried out to investigate the evolution of CV-A4 and understand the spatiotemporal diffusion around the world using BEAST and SPREAD software. Phylogenetic trees showed that CV-A4 emerged to be more active in recent decades and multiple transmission chains were co-circulating. The molecular clock analysis estimated a mean evolutionary rate of 6.4×10 substitutions/site/year, and the estimated origin of CV-A4 around 1944. The phylogeographic analyses suggested the origin of CV-A4 could be in the USA, however regional dissemination was mainly located around the Asia-Europe region. The spatiotemporal dynamics of CV-A4 exhibited frequent viral traffic among localities, and virus from Shandong province seemed to have played a central role in spreading around China and neighboring countries. Our phylogenetic description and phylogeographic analyses indicate the importance of large spatial- and temporal-scale studies in understanding epidemiological dynamics of CV-A4, particularly the diffusion routes will be of great importance to global control efforts.
[Mh] Termos MeSH primário: Enterovirus/classificação
[Mh] Termos MeSH secundário: Ásia
Teorema de Bayes
Proteínas do Capsídeo/química
Proteínas do Capsídeo/genética
China
Infecções por Coxsackievirus/diagnóstico
Infecções por Coxsackievirus/transmissão
Infecções por Coxsackievirus/virologia
Enterovirus/genética
Europa (Continente)
Seres Humanos
Tipagem Molecular
Filogenia
Filogeografia
RNA Viral/isolamento & purificação
RNA Viral/metabolismo
Análise Espaço-Temporal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (RNA, Viral)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170925
[St] Status:MEDLINE


  4 / 12579 MEDLINE  
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[PMID]:28456575
[Au] Autor:Grzesik P; MacMath D; Henson B; Prasad S; Joshi P; Desai PJ
[Ad] Endereço:Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, Baltimore, MD, USA.
[Ti] Título:Incorporation of the Kaposi's sarcoma-associated herpesvirus capsid vertex-specific component (CVSC) into self-assembled capsids.
[So] Source:Virus Res;236:9-13, 2017 05 15.
[Is] ISSN:1872-7492
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Self-assembly of herpesvirus capsids can be accomplished in heterologous expression systems provided all six capsid proteins are present. We have demonstrated the assembly of icosahedral Kaposi's sarcoma-associated herpesvirus (KSHV) capsids in insect cells using the baculovirus expression system. Using this self-assembly system we investigated whether we could add additional capsid associated proteins and determine their incorporation into the assembled capsid. We chose the capsid vertex-specific component (CVSC) proteins encoded by open reading frames (ORFs) 19 and 32 to test this. This complex sits on the capsid vertex and is important for capsid maturation in herpesvirus-infected cells. Co-immunoprecipitation assays were used to initially confirm a bi-molecular interaction between ORF19 and ORF32. Both proteins also precipitated the triplex proteins of the capsid shell (ORF26 and ORF62) as well as the major capsid protein (ORF25). Capsid immunoprecipitation assays revealed the incorporation of ORF19 as well as ORF32 into assembled capsids. Similar experiments also showed that the incorporation of each protein occurred independent of the other. These studies reveal biochemically how the KSHV CVSC interacts with the capsid shell.
[Mh] Termos MeSH primário: Capsídeo/metabolismo
Herpesvirus Humano 8/fisiologia
Sarcoma de Kaposi/virologia
Proteínas Virais/metabolismo
Montagem de Vírus
[Mh] Termos MeSH secundário: Proteínas do Capsídeo/genética
Proteínas do Capsídeo/metabolismo
Herpesvirus Humano 8/genética
Seres Humanos
Fases de Leitura Aberta
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (Viral Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  5 / 12579 MEDLINE  
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[PMID]:29304063
[Au] Autor:Ataie Kachoie E; Behjatnia SAA; Kharazmi S
[Ad] Endereço:Institute of Biotechnology, Shiraz University, Shiraz, Iran.
[Ti] Título:Expression of Human Immunodeficiency Virus type 1 (HIV-1) coat protein genes in plants using cotton leaf curl Multan betasatellite-based vector.
[So] Source:PLoS One;13(1):e0190403, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It has already been demonstrated that a betasatellite associated with cotton leaf curl Multan virus (CLCuMB) can be used as a plant and animal gene delivery vector to plants. To examine the ability of CLCuMB as a tool to transfer coat protein genes of HIV-1 to plants, two recombinant CLCuMB constructs in which the CLCuMB ßC1 ORF was replaced with two HIV-1 genes fractions including a 696 bp DNA fragment related to the HIV-1 p24 gene and a 1501 bp DNA fragment related to the HIV-1 gag gene were constructed. Gag is the HIV-1 coat protein gene and p24 is a component of the particle capsid. Gag and p24 are used for vaccine production. Recombinant constructs were inoculated to Nicotiana glutinosa and N. benthamiana plants in the presence of an Iranian isolate of Tomato yellow leaf curl virus (TYLCV-[Ab]) as a helper virus. PCR analysis of inoculated plants indicated that p24 gene was successfully replicated in inoculated plants, but the gag gene was not. Real-time PCR and ELISA analysis of N. glutinosa and N. benthamiana plants containing the replicative forms of recombinant construct of CLCuMB/p24 indicated that p24 was expressed in these plants. This CLCuMB-based expression system offers the possibility of mass production of recombinant HIV-1 p24 protein in plants.
[Mh] Termos MeSH primário: Begomovirus/genética
Proteínas do Capsídeo/genética
DNA Satélite/genética
Vetores Genéticos
HIV-1/genética
[Mh] Termos MeSH secundário: Begomovirus/patogenicidade
Ensaio de Imunoadsorção Enzimática
Fases de Leitura Aberta
Reação em Cadeia da Polimerase
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (DNA, Satellite)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190403


  6 / 12579 MEDLINE  
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[PMID]:29214362
[Au] Autor:Zhuo T; Zhu LJ; Lu CC; Jiang CY; Chen ZY; Zhang G; Wang ZH; Jovel J; Han YH
[Ad] Endereço:College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
[Ti] Título:Complete nucleotide sequence of jasmine virus H, a new member of the family Tombusviridae.
[So] Source:Arch Virol;163(3):731-735, 2018 Mar.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Jasmine virus H (JaVH) is a novel virus associated with symptoms of yellow mosaic on jasmine. The JaVH genome is 3,867 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on genomic and phylogenetic analysis, JaVH is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.
[Mh] Termos MeSH primário: Genoma Viral
Jasminum/virologia
Filogenia
RNA Viral/genética
Tombusviridae/genética
[Mh] Termos MeSH secundário: Sequência de Bases
Proteínas do Capsídeo/genética
Sequenciamento de Nucleotídeos em Larga Escala
Fases de Leitura Aberta
RNA Replicase/genética
Tombusviridae/classificação
Tombusviridae/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (RNA, Viral); EC 2.7.7.48 (RNA Replicase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3663-z


  7 / 12579 MEDLINE  
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[PMID]:29196818
[Au] Autor:Kikuchi W; Nakagomi T; Gauchan P; Agbemabiese CA; Noguchi A; Nakagomi O; Takahashi T
[Ad] Endereço:Department of Paediatrics, Akita University Graduate School of Medicine, Akita, Japan.
[Ti] Título:Detection in Japan of an equine-like G3P[8] reassortant rotavirus A strain that is highly homologous to European strains across all genome segments.
[So] Source:Arch Virol;163(3):791-794, 2018 Mar.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Equine-like G3P[8] rotavirus A strains with DS-1-like backbone genes have emerged since 2013. An equine-like RVA/Human-wt/JPN/15R429/2015/G3P[8] strain possessing I2-R2-C2-M2-A2-N2-T2-E2-H2 was detected in Japan in 2015. Its VP7 gene was ≥ 99.3% identical to those of equine-like G3P[4] strains detected in Japan, and the remaining 10 genes were 98.6-99.8% identical to G1P[8] double-gene reassortants detected in Japan, Thailand and the Philippines. Thus, 15R429 was likely generated through reassortment between the equine-like G3P[4] and G1P[8] reassortant strains. Notably, 15R429 was 98.5-99.8% identical across all 11 genes of the equine-like G3P[8] strains detected in Spain and Hungary in 2015.
[Mh] Termos MeSH primário: Antígenos Virais/genética
Proteínas do Capsídeo/genética
Gastroenterite/veterinária
Doenças dos Cavalos/epidemiologia
Filogenia
Vírus Reordenados/genética
Infecções por Rotavirus/veterinária
Rotavirus/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Europa (Continente)/epidemiologia
Gastroenterite/epidemiologia
Gastroenterite/virologia
Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Doenças dos Cavalos/virologia
Cavalos/virologia
Seres Humanos
Japão/epidemiologia
Vírus Reordenados/classificação
Vírus Reordenados/isolamento & purificação
Rotavirus/classificação
Rotavirus/isolamento & purificação
Infecções por Rotavirus/epidemiologia
Infecções por Rotavirus/virologia
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral); 0 (Capsid Proteins); 0 (VP7 protein, Rotavirus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171203
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3668-7


  8 / 12579 MEDLINE  
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[PMID]:29355529
[Au] Autor:Wang X; Wang JG; Geng YY; Wang JJ; Zhang XM; Yang SS; Jiang W; Liu WQ
[Ad] Endereço:State Key Laboratories of Agrobiotechnology, College of Biological Sciences, China Agricultural University, PR China.
[Ti] Título:An enhanced anti-tumor effect of apoptin-cecropin B on human hepatoma cells by using bacterial magnetic particle gene delivery system.
[So] Source:Biochem Biophys Res Commun;496(2):719-725, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The gene therapy of cancer, due to the limit of its efficiency and safety, has not been widely used in clinical. Recently, bacterial magnetic particles (BMPs), which are membrane-bound nanocrystals found in magnetotactic bacteria, have been exploited as a new gene delivery system. However, its application on gene therapy remains to be explored. In our previous study, we found that a combination of cecropin B (ABPs) and apoptin (VP3) could serve as an effective gene therapeutic agent. Thus, in this study, we used BMPs to deliver the co-expression plasmid of these two gene, namely pVAX1-VA, and evaluated its therapeutic effect on human hepatocellular carcinoma (HepG2). Our results showed that BMPs significantly improved the efficiency of gene transfection (almost 3-fold than Lipofectamine 2000 at 48 h, P < .001), which led to stronger apoptosis (in a peak almost 2-fold than Lipofectamine 2000-pVAX1-VA, P < .01) and growth inhibition of HepG2 cells. More importantly, compared with Lipofectamine 2000-pVAX1-VA group, BMP-pVAX1-VA strikingly inhibited tumor growth (0.60 ±â€¯0.09 g vs. 0.88 ±â€¯0.11 g, P < .05) in nude mouse tumor models and increased the tumor-infiltrating lymphocytes considerably without apparent cytotoxicity. These findings suggest that BMPs could be an attractive gene delivery system for gene therapy and provide a potential available treatment for human hepatocellular carcinoma and maybe some other kinds of tumors.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/genética
Carcinoma Hepatocelular/terapia
Técnicas de Transferência de Genes
Vetores Genéticos/administração & dosagem
Proteínas de Insetos/genética
Neoplasias Hepáticas/terapia
Magnetossomos/química
Magnetospirillum/química
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/metabolismo
Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/patologia
Portadores de Fármacos/química
Feminino
Terapia Genética/métodos
Vetores Genéticos/genética
Vetores Genéticos/uso terapêutico
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/patologia
Camundongos Endogâmicos BALB C
Camundongos Nus
Transfecção/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Capsid Proteins); 0 (Drug Carriers); 0 (Insect Proteins); 0 (VP3 protein, Chicken anemia virus); 80451-05-4 (cecropin B protein, Insecta)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


  9 / 12579 MEDLINE  
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[PMID]:29300751
[Au] Autor:Ohshima K; Mitoma S; Gibbs AJ
[Ad] Endereço:Laboratory of Plant Virology, Department of Applied Biological Sciences, Faculty of Agriculture, Saga University, Saga, Japan.
[Ti] Título:The genetic diversity of narcissus viruses related to turnip mosaic virus blur arbitrary boundaries used to discriminate potyvirus species.
[So] Source:PLoS One;13(1):e0190511, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Narcissus plants (Narcissus tazetta var. chinensis) showing mosaic or striping leaves were collected from around Japan, and tested for virus infections using potyvirus-specific primers. Many were found to be infected with a macluravirus and mixtures of different potyviruses, one third of them narcissus yellow stripe virus (NYSV)-like viruses. Genomes of nine of the NYSV-like viruses were sequenced and, together with four already published, provided data for phylogenetic and pairwise identity analyses of their place in the turnip mosaic virus (TuMV) phylogenetic group. Using existing ICTV criteria for defining potyvirus species, the narcissus viruses in TuMV group were found to be from five species; the previously described NLSYV, and four new species we call narcissus virus 1 (NV-1) and narcissus yellow stripe-1 to -3 (NYSV-1, NYSV-2 and NYSV-3). However, as all are from a single host species, and natural recombinants with NV-1 and NYSV-3 'parents have been found in China and India, we also conclude that they could be considered to be members of a single mega-species, narcissus virus; the criteria for defining such a potyvirus species would then be that their polyprotein sequences have greater than 69% identical nucleotides and greater than 75% identical amino acids.
[Mh] Termos MeSH primário: Variação Genética
Narcissus/virologia
Potyvirus/genética
[Mh] Termos MeSH secundário: Proteínas do Capsídeo/genética
Genes Virais
Filogenia
Potyvirus/classificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Capsid Proteins)
[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.0190511


  10 / 12579 MEDLINE  
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[PMID]:28450058
[Au] Autor:Edwards TC; Lomonosova E; Patel JA; Li Q; Villa JA; Gupta AK; Morrison LA; Bailly F; Cotelle P; Giannakopoulou E; Zoidis G; Tavis JE
[Ad] Endereço:Department of Molecular Microbiology and Immunology and Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO, USA; Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO, USA. Electronic address: edwardstc@slu.edu.
[Ti] Título:Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and related polyoxygenated heterocycles.
[So] Source:Antiviral Res;143:205-217, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We previously reported low sensitivity of the hepatitis B virus (HBV) ribonuclease H (RNaseH) enzyme to inhibition by N-hydroxyisoquinolinedione (HID) compounds. Subsequently, our biochemical RNaseH assay was found to have a high false negative rate for predicting HBV replication inhibition, leading to underestimation of the number of HIDs that inhibit HBV replication. Here, 39 HID compounds and structurally related polyoxygenated heterocycles (POH), N-hydroxypyridinediones (HPD), and flutimides were screened for inhibition of HBV replication in vitro. Inhibiting the HBV RNaseH preferentially blocks synthesis of the positive-polarity DNA strand and causes accumulation of RNA:DNA heteroduplexes. Eleven HIDs and one HPD preferentially inhibited HBV positive-polarity DNA strand accumulation. EC s ranged from 0.69 µM to 19 µM with therapeutic indices from 2.4 to 71. Neither the HIDs nor the HPD had an effect on the ability of the polymerase to elongate DNA strands in capsids. HBV RNaseH inhibition by the HIDs was confirmed with an improved RNaseH assay and by detecting accumulation RNA:DNA heteroduplexes in HBV capsids from cells treated with a representative HID. Therefore, the HID scaffold is more promising for anti-HBV drug discovery than we originally reported, and the HPD scaffold may hold potential for antiviral development. The preliminary structure-activity relationship will guide optimization of the HID/HPDs as HBV inhibitors.
[Mh] Termos MeSH primário: Antivirais/antagonistas & inibidores
Antivirais/química
Vírus da Hepatite B/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antivirais/administração & dosagem
Proteínas do Capsídeo/genética
Linhagem Celular Tumoral
Cercopithecus aethiops
Replicação do DNA/efeitos dos fármacos
DNA Viral/efeitos dos fármacos
Descoberta de Drogas
Avaliação Pré-Clínica de Medicamentos
Hepatite B/virologia
Vírus da Hepatite B/enzimologia
Vírus da Hepatite B/genética
Vírus da Hepatite B/fisiologia
Seres Humanos
Testes de Sensibilidade Microbiana
Piperazinas/farmacologia
Ribonuclease H/efeitos dos fármacos
Relação Estrutura-Atividade
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Capsid Proteins); 0 (DNA, Viral); 0 (Piperazines); 162666-34-4 (flutimide); EC 3.1.26.4 (Ribonuclease H); EC 3.1.26.4 (ribonuclease HI)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE



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