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[PMID]:27535044
[Au] Autor:Caridi F; Cañas-Arranz R; Vázquez-Calvo A; Sobrino F; Martín-Acebes MA
[Ad] Endereço:Department of Virology and Microbiology, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
[Ti] Título:Equine Rhinitis A Virus Mutants with Altered Acid Resistance Unveil a Key Role of VP3 and Intrasubunit Interactions in the Control of the pH Stability of the Aphthovirus Capsid.
[So] Source:J Virol;90(21):9725-9732, 2016 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Equine rhinitis A virus (ERAV) is a picornavirus associated with respiratory disease in horses and is genetically closely related to foot-and-mouth disease virus (FMDV), the prototype aphthovirus. ERAV has recently gained interest as an FMDV alternative for the study of aphthovirus biology, including cell entry and uncoating or antiviral testing. As described for FMDV, current data support that acidic pH inside cellular endosomes triggers ERAV uncoating. In order to provide further insights into aphthovirus uncoating mechanism, we have isolated a panel of ERAV mutants with altered acid sensitivity and that differed on their degree of sensitivity to the inhibition of endosome acidification. These results provide functional evidence of the involvement of acidic pH on ERAV uncoating within endosomes. Remarkably, all amino acid substitutions found in acid-labile or acid-resistant ERAVs were located in the capsid protein VP3, indicating that this protein plays a pivotal role for the control of pH stability of the ERAV capsid. Moreover, all amino acid substitutions mapped at the intraprotomer interface between VP3 and VP2 or between VP3 and the N terminus of VP1. These results expand our knowledge on the regions that regulate the acid stability of aphthovirus capsid and should be taken into account when using ERAV as a surrogate of FMDV. IMPORTANCE: The viral capsid constitutes a sort of dynamic nanomachine that protects the viral genome against environmental assaults while accomplishing important functions such as receptor attachment for viral entry or genome release. We have explored the molecular determinants of aphthovirus capsid stability by isolating and characterizing a panel of equine rhinitis A virus mutants that differed on their acid sensitivity. All the mutations were located within a specific region of the capsid, the intraprotomer interface among capsid proteins, thus providing new insights into the regions that control the acid stability of aphthovirus capsid. These findings could positively contribute to the development of antiviral approaches targeting aphthovirus uncoating or the refinement of vaccine strategies based on capsid stabilization.
[Mh] Termos MeSH primário: Ácidos/metabolismo
Aphthovirus/genética
Proteínas do Capsídeo/genética
Cavalos/virologia
[Mh] Termos MeSH secundário: Substituição de Aminoácidos/genética
Animais
Antivirais/farmacologia
Aphthovirus/efeitos dos fármacos
Capsídeo/efeitos dos fármacos
Endossomos/virologia
Vírus da Febre Aftosa/efeitos dos fármacos
Genoma Viral/genética
Concentração de Íons de Hidrogênio
Mutação/genética
Infecções por Picornaviridae/tratamento farmacológico
Infecções por Picornaviridae/virologia
Internalização do Vírus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acids); 0 (Antiviral Agents); 0 (Capsid Proteins); 0 (VP3 protein, Foot-and-mouth disease virus)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE


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[PMID]:25789939
[Au] Autor:Hause BM; Collin EA; Anderson J; Hesse RA; Anderson G
[Ad] Endereço:Veterinary Diagnostic Laboratory and Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, United States of America.
[Ti] Título:Bovine rhinitis viruses are common in U.S. cattle with bovine respiratory disease.
[So] Source:PLoS One;10(3):e0121998, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5'-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.
[Mh] Termos MeSH primário: Aphthovirus/genética
Aphthovirus/fisiologia
Doenças dos Bovinos/epidemiologia
Infecções por Picornaviridae/veterinária
Infecções Respiratórias/veterinária
[Mh] Termos MeSH secundário: Animais
Aphthovirus/classificação
Bovinos
Doenças dos Bovinos/sangue
Doenças dos Bovinos/virologia
Genômica
Epidemiologia Molecular
Dados de Sequência Molecular
Filogenia
Infecções por Picornaviridae/sangue
Infecções por Picornaviridae/epidemiologia
Infecções Respiratórias/sangue
Infecções Respiratórias/epidemiologia
Infecções Respiratórias/virologia
Análise de Sequência
Estudos Soroepidemiológicos
Inquéritos e Questionários
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150325
[Lr] Data última revisão:
150325
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150320
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0121998


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[PMID]:24648455
[Au] Autor:Bakker SE; Groppelli E; Pearson AR; Stockley PG; Rowlands DJ; Ranson NA
[Ad] Endereço:Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
[Ti] Título:Limits of structural plasticity in a picornavirus capsid revealed by a massively expanded equine rhinitis A virus particle.
[So] Source:J Virol;88(11):6093-9, 2014 Jun.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The Picornaviridae family of small, nonenveloped viruses includes major pathogens of humans and animals. They have positive-sense, single-stranded RNA genomes, and the mechanism(s) by which these genomes are introduced into cells to initiate infection remains poorly understood. The structures of presumed uncoating intermediate particles of several picornaviruses show limited expansion and some increased porosity compared to the mature virions. Here, we present the cryo-electron microscopy structure of native equine rhinitis A virus (ERAV), together with the structure of a massively expanded ERAV particle, each at ∼17-Šresolution. The expanded structure has large pores on the particle 3-fold axes and has lost the RNA genome and the capsid protein VP4. The expanded structure thus illustrates both the limits of structural plasticity in such capsids and a plausible route by which genomic RNA might exit. IMPORTANCE: Picornaviruses are important animal and human pathogens that protect their genomic RNAs within a protective protein capsid. Upon infection, this genomic RNA must be able to leave the capsid to initiate a new round of infection. We describe here the structure of a unique, massively expanded state of equine rhinitis A virus that provides insight into how this exit might occur.
[Mh] Termos MeSH primário: Aphthovirus/química
Capsídeo/química
Modelos Moleculares
Conformação Molecular
Picornaviridae/química
Vírion/ultraestrutura
[Mh] Termos MeSH secundário: Aphthovirus/ultraestrutura
Microscopia Crioeletrônica
Processamento de Imagem Assistida por Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1407
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140321
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.01979-13


  4 / 2338 MEDLINE  
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[PMID]:24583031
[Au] Autor:Osiceanu AM; Murao LE; Kollanur D; Swinnen J; De Vleeschauwer AR; Lefebvre DJ; De Clercq K; Neyts J; Goris N
[Ad] Endereço:Okapi Sciences NV, Ambachtenlaan 1, 3001 Heverlee, Belgium.
[Ti] Título:In vitro surrogate models to aid in the development of antivirals for the containment of foot-and-mouth disease outbreaks.
[So] Source:Antiviral Res;105:59-63, 2014 May.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Foot-and-mouth disease virus (FMDV) is a highly pathogenic member of the genus Aphthovirus (family Picornaviridae) that is only to be manipulated in high-containment facilities, thus complicating research on and discovery of antiviral strategies against the virus. Bovine rhinitis B virus (BRBV) and equine rhinitis A virus (ERAV), phylogenetically most closely related to FMDV, were explored as surrogates for FMDV in antiviral studies. Although no efficient cell culture system has been reported so far for BRBV, we demonstrate that infection of primary bovine kidney cells resulted in an extensive but rather poorly-reproducible induction of cytopathic effect (CPE). Madin-Darby bovine kidney cells on the other hand supported viral replication in the absence of CPE. Antiviral tests were developed for ERAV in Vero A cells employing a viral RNA-reduction assay and CPE-reduction assay; the latter having a Z' factor of 0.83±0.07. The BRBV and ERAV models were next used to assess the anti-aphthovirus activity of two broad-spectrum antiviral agents 2'-C-methylcytidine (2CMC) and ribavirin, as well as of the enterovirus-specific inhibitor enviroxime. The effects of the three compounds in the CPE-reduction (ERAV) and viral RNA-reduction assays (BRBV and ERAV) were comparable. Akin to 2CMC, compound A, a recently-discovered non-nucleoside pan-serotype FMDV inhibitor, also inhibited the replication of both BRBV and ERAV, whereas enviroxime was devoid of activity. The BRBV and ERAV surrogate models reported here can be manipulated in BSL-2 laboratories and may facilitate studies to unravel the mechanism of action of novel FMDV inhibitors.
[Mh] Termos MeSH primário: Antivirais/isolamento & purificação
Antivirais/farmacologia
Aphthovirus/efeitos dos fármacos
Descoberta de Drogas/métodos
[Mh] Termos MeSH secundário: Animais
Benzimidazóis/farmacologia
Bovinos
Linhagem Celular
Cercopithecus aethiops
Citidina/análogos & derivados
Citidina/farmacologia
Efeito Citopatogênico Viral/efeitos dos fármacos
Febre Aftosa/tratamento farmacológico
Modelos Teóricos
RNA Viral/análise
Ribavirina/farmacologia
Cultura de Vírus/métodos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Benzimidazoles); 0 (RNA, Viral); 133013L556 (enviroxime); 27FS20C1D8 (2'-C-methylcytidine); 49717AWG6K (Ribavirin); 5CSZ8459RP (Cytidine)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:140421
[Lr] Data última revisão:
140421
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140304
[St] Status:MEDLINE


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[PMID]:24471753
[Au] Autor:Diaz-Méndez A; Hewson J; Shewen P; Nagy E; Viel L
[Ad] Endereço:Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada., Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada.
[Ti] Título:Characteristics of respiratory tract disease in horses inoculated with equine rhinitis A virus.
[So] Source:Am J Vet Res;75(2):169-78, 2014 Feb.
[Is] ISSN:1943-5681
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To develop a method for experimental induction of equine rhinitis A virus (ERAV) infection in equids and to determine the clinical characteristics of such infection. ANIMALS: 8 ponies (age, 8 to 12 months) seronegative for antibodies against ERAV. PROCEDURES-Nebulization was used to administer ERAV (strain ERAV/ON/05; n = 4 ponies) or cell culture medium (control ponies; 4) into airways of ponies; 4 previously ERAV-inoculated ponies were reinoculated 1 year later. Physical examinations and pulmonary function testing were performed at various times for 21 days after ERAV or mock inoculation. Various types of samples were obtained for virus isolation, blood samples were obtained for serologic testing, and clinical scores were determined for various variables. RESULTS: ERAV-inoculated ponies developed respiratory tract disease characterized by pyrexia, nasal discharge, adventitious lung sounds, and enlarged mandibular lymph nodes. Additionally, these animals had purulent mucus in lower airways up to the last evaluation time 21 days after inoculation (detected endoscopically). The virus was isolated from various samples obtained from lower and upper airways of ERAV-inoculated ponies up to 7 days after exposure; this time corresponded with an increase in serum titers of neutralizing antibodies against ERAV. None of the ponies developed clinical signs of disease after reinoculation 1 year later. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated ERAV induced respiratory tract disease in seronegative ponies. However, ponies with neutralizing antibodies against ERAV did not develop clinical signs of disease when reinoculated with the virus. Therefore, immunization of ponies against ERAV could prevent respiratory tract disease attributable to that virus in such animals.
[Mh] Termos MeSH primário: Aphthovirus
Doenças dos Cavalos/virologia
Infecções por Picornaviridae/veterinária
Doenças Respiratórias/veterinária
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Aphthovirus/imunologia
Temperatura Corporal
Doenças dos Cavalos/imunologia
Doenças dos Cavalos/patologia
Cavalos
Infecções por Picornaviridae/imunologia
Infecções por Picornaviridae/patologia
Infecções por Picornaviridae/virologia
Doenças Respiratórias/imunologia
Doenças Respiratórias/patologia
Doenças Respiratórias/virologia
Testes Sorológicos/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral)
[Em] Mês de entrada:1409
[Cu] Atualização por classe:140129
[Lr] Data última revisão:
140129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140130
[St] Status:MEDLINE
[do] DOI:10.2460/ajvr.75.2.169


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[PMID]:24337965
[Au] Autor:Lange J; Groth M; Fichtner D; Granzow H; Keller B; Walther M; Platzer M; Sauerbrei A; Zell R
[Ad] Endereço:Department of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University, Hans Knoell Str. 2, 07745 Jena, Germany.
[Ti] Título:Virus isolate from carp: genetic characterization reveals a novel picornavirus with two aphthovirus 2A-like sequences.
[So] Source:J Gen Virol;95(Pt 1):80-90, 2014 Jan.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Picornaviruses have been isolated from a variety of hosts, mainly mammals and birds. Here, we describe the sequence analysis of carp picornavirus 1 (CPV-1) F37/06 that was isolated from an organ pool (heart, brain, liver) of a common carp (Cyprinus carpio). This carp perished after an accidental discharge of liquid manure into a fish pond and presented without obvious clinical symptoms. Experimental intraperitoneal infection of young carp with CPV-1 revealed no clinical signs, but the virus was re-isolated from various organs. Sequence analysis of almost the complete genome (7632 nt excluding the poly-A tract) revealed a novel picornavirus clade. In phylogenetic trees, the polymerase sequence clusters with parechoviruses, duck hepatitis A virus, eel picornavirus and aquamavirus A. The ORF includes 6807 nt and encodes a polyprotein of 2269 amino acids. CPV-1 has a genome layout like that of picornaviruses except for the presence of two aphthovirus 2A-like NPGP sequence motifs: VPg+5'UTR[1AB-1C-1D-2A1(npgp)/2A2(npgp)-2B-2C(ATPase)/3A-3B(VPg)-3C(pro)-3D(pol)]3'UTR-poly-A. 2A1(npgp) and 2A2(npgp) are separated by 133 amino acids. The proteins 2A2(npgp), 2B, 3A and 3B(VPg) have no significant similarity to the corresponding proteins of other picornaviruses. Amino acid identities of the orthologous proteins P1, 2C, 3C(pro) and 3D(pol) range from 16.4 to 40.8 % in the eel picornavirus/CPV-1 comparison. 3D(pol) shows the closest similarity to eel picornavirus, with an amino acid identity of 40.8 %, followed by human parechovirus (36.5 %), duck hepatitis A virus (32.7 %) and swine pasivirus (29.3 %). Both the unique genome organization and low sequence similarity support the assignment of CPV-1 to a novel picornavirus species within a novel genus.
[Mh] Termos MeSH primário: Aphthovirus/genética
Carpas/virologia
Doenças dos Peixes/virologia
Infecções por Picornaviridae/veterinária
Picornaviridae/genética
Picornaviridae/isolamento & purificação
[Mh] Termos MeSH secundário: Regiões 5' não Traduzidas
Sequência de Aminoácidos
Animais
Aphthovirus/química
Aphthovirus/classificação
Genoma Viral
Seres Humanos
Dados de Sequência Molecular
Fases de Leitura Aberta
Filogenia
Picornaviridae/química
Picornaviridae/classificação
Infecções por Picornaviridae/virologia
Alinhamento de Sequência
Proteínas Virais/química
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Viral Proteins)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:131216
[Lr] Data última revisão:
131216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131217
[St] Status:MEDLINE
[do] DOI:10.1099/vir.0.058172-0


  7 / 2338 MEDLINE  
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[PMID]:24210112
[Au] Autor:Uddowla S; Pacheco JM; Larson C; Bishop E; Rodriguez LL; Rai DK; Arzt J; Rieder E
[Ad] Endereço:Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, United States.
[Ti] Título:Characterization of a chimeric foot-and-mouth disease virus bearing a bovine rhinitis B virus leader proteinase.
[So] Source:Virology;447(1-2):172-80, 2013 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bovine rhinitis B virus (BRBV) shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). This study examined if the BRBV leader proteinase (L(pro) ) could functionally replace that of FMDV. A mutant A24LBRV3DYR FMDV engineered with the BRBV L(pro) and an antigenic marker in the 3D polymerase exhibited growth properties and eIF4G cleavage similar to parental A24WT virus. The A24LBRV3DYR type I interferon activity in infected bovine cells resembled that of A24LL virus that lacks L(pro), but this effect was less pronounced for A24LBRV3DYR infected porcine cells. In vivo studies showed that the A24LBRV3DYR virus was attenuated in cattle, and exhibited low virulence in pigs exposed by direct contact. The mutant virus induced protective immunity in cattle against challenge with parental A24WT. These results provide evidence that L(pro) of different Aphthoviruses are not fully functionally interchangeable and have roles that may depend on the nature of the infected host.
[Mh] Termos MeSH primário: Aphthovirus/genética
Endopeptidases/genética
Vírus da Febre Aftosa/genética
[Mh] Termos MeSH secundário: Animais
Bovinos
Doenças dos Bovinos/patologia
Doenças dos Bovinos/prevenção & controle
Doenças dos Bovinos/virologia
Linhagem Celular
Endopeptidases/metabolismo
Fator de Iniciação 4G em Eucariotos/metabolismo
Febre Aftosa/patologia
Febre Aftosa/virologia
Vírus da Febre Aftosa/crescimento & desenvolvimento
Vírus da Febre Aftosa/fisiologia
Modelos Moleculares
Conformação Proteica
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Suínos
Doenças dos Suínos/patologia
Doenças dos Suínos/virologia
Vacinas Atenuadas/administração & dosagem
Vacinas Atenuadas/genética
Vacinas Atenuadas/imunologia
Ensaio de Placa Viral
Vacinas Virais/administração & dosagem
Vacinas Virais/genética
Vacinas Virais/imunologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-4G); 0 (Recombinant Proteins); 0 (Vaccines, Attenuated); 0 (Viral Vaccines); EC 3.4.- (Endopeptidases); EC 3.4.99.- (leader proteinase, foot-and-mouth disease virus)
[Em] Mês de entrada:1401
[Cu] Atualização por classe:131111
[Lr] Data última revisão:
131111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131112
[St] Status:MEDLINE


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[PMID]:24125297
[Au] Autor:Cermelli P; Indelicato G; Twarock R
[Ad] Endereço:Dipartimento di Matematica, Università di Torino, Torino, Italy.
[Ti] Título:Nonicosahedral pathways for capsid expansion.
[So] Source:Phys Rev E Stat Nonlin Soft Matter Phys;88(3):032710, 2013 Sep.
[Is] ISSN:1550-2376
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:For a significant number of viruses a structural transition of the protein container that encapsulates the viral genome forms an important part of the life cycle and is a prerequisite for the particle becoming infectious. Despite many recent efforts the mechanism of this process is still not fully understood, and a complete characterization of the expansion pathways is still lacking. We present here a coarse-grained model that captures the essential features of the expansion process and allows us to investigate the conditions under which a viral capsid becomes unstable. Based on this model we demonstrate that the structural transitions in icosahedral viral capsids are likely to occur through a low-symmetry cascade of local expansion events spreading in a wavelike manner over the capsid surface.
[Mh] Termos MeSH primário: Capsídeo/química
Modelos Moleculares
[Mh] Termos MeSH secundário: Aphthovirus
Capsídeo/metabolismo
Proteínas do Capsídeo/química
Proteínas do Capsídeo/metabolismo
Propriedades de Superfície
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Capsid Proteins)
[Em] Mês de entrada:1405
[Cu] Atualização por classe:131015
[Lr] Data última revisão:
131015
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131016
[St] Status:MEDLINE


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[PMID]:23698740
[Au] Autor:Arber C; Abhyankar H; Heslop HE; Brenner MK; Liu H; Dotti G; Savoldo B
[Ad] Endereço:Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX 77030, USA.
[Ti] Título:The immunogenicity of virus-derived 2A sequences in immunocompetent individuals.
[So] Source:Gene Ther;20(9):958-62, 2013 Sep.
[Is] ISSN:1476-5462
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Genetic engineering of T cells for adoptive immunotherapy in cancer patients has shown significant promise. To ensure optimal antitumor activity and safety, the simultaneous expression of multiple genes is frequently required, and short viral-derived 2A sequences are increasingly preferred for this purpose. Concerns exist, however, that these virus-derived sequences may induce unwanted immune responses, and thus diminish persistence of the gene-modified cells after adoptive transfer. Whereas such responses were absent in immunocompromised recipients, potential immunogenicity in immunocompetent individuals remains a concern. We now address whether ex vivo T cell responses can be elicited against the most widely used 2A sequences (2A-Thosea asigna virus (TAV) or 2A-equine rhinitis virus (ERAV), specifically) in immunocompetent individuals. We used a potent ex vivo culture system previously validated to induce T cell responses even against weakly immunogenic antigens. Of the sixteen donors tested, only five released very low levels of interferon-γ in response to 2A-TAV peptide mixtures (single peptide specificity in three donors, adjacent self-antigen peptide specificity in one donor and nonspecific reactivity in one donor). None of them produced cytotoxic activity or responded to 2A-ERAV. These results suggest that exposure to viral-derived 2A sequences is unlikely to produce unwanted T cell responses in immunocompetent individuals and further supports their continued use for studies of human gene therapy.
[Mh] Termos MeSH primário: Aphthovirus/imunologia
Peptídeos/imunologia
Vírus de RNA/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Antígenos/imunologia
Aphthovirus/genética
Linhagem Celular
Vetores Genéticos
Voluntários Saudáveis
Seres Humanos
Imunocompetência
Imunoterapia Adotiva
Interferon gama/biossíntese
Interferon gama/imunologia
Ativação Linfocitária
Dados de Sequência Molecular
Peptídeos/química
Vírus de RNA/genética
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antigens); 0 (Peptides); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130524
[St] Status:MEDLINE
[do] DOI:10.1038/gt.2013.25


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[PMID]:23594411
[Au] Autor:Oguma K; Ishida M; Maeda K; Sentsui H
[Ad] Endereço:Laboratory of Veterinary Epizootiology, Department of Veterinary Medicine, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan.
[Ti] Título:Efficient propagation of equine viruses in a newly established equine cell line, FHK-13.1 cells.
[So] Source:J Vet Med Sci;75(9):1223-5, 2013.
[Is] ISSN:1347-7439
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Equine cells are required for isolation of viruses that infect the horse. However, only a few equine cell lines and cell cultures are available so far. Fetal horse kidney (FHK)-Tcl3.1 cell is a novel cell line established by introducing simian virus 40 (SV40) large T antigen. In the present study, the ability to propagate equine viruses was compared between FHK-Tcl3.1 cells and other equine cells. FHK-Tcl3.1 cells efficiently increased many viruses derived from or having pathogenicity to horses and produced high infective titers in culture fluids. These results indicate that FHK-Tcl3.1 cells would be useful for propagation and serological tests of viruses that affect Equidae.
[Mh] Termos MeSH primário: Linhagem Celular/virologia
Feto/citologia
Cavalos/virologia
Rim/citologia
[Mh] Termos MeSH secundário: Adenoviridae
Animais
Antígenos Virais de Tumores
Aphthovirus
Técnicas de Cultura de Células/veterinária
Linhagem Celular/citologia
Efeito Citopatogênico Viral
Vírus 40 dos Símios
Varicellovirus
Vesiculovirus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral, Tumor)
[Em] Mês de entrada:1409
[Cu] Atualização por classe:161018
[Lr] Data última revisão:
161018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130419
[St] Status:MEDLINE



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