Base de dados : MEDLINE
Pesquisa : G06.920.913 [Categoria DeCS]
Referências encontradas : 852 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 86 ir para página                         

  1 / 852 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28461070
[Au] Autor:Albulescu IC; Kovacikova K; Tas A; Snijder EJ; van Hemert MJ
[Ad] Endereço:Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
[Ti] Título:Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles.
[So] Source:Antiviral Res;143:230-236, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is a mosquito-borne flavivirus that mostly causes asymptomatic infections or mild disease characterized by low-grade fever, rash, conjunctivitis, and malaise. However, the recent massive ZIKV epidemics in the Americas have also linked ZIKV infection to fetal malformations like microcephaly and Guillain-Barré syndrome in adults, and have uncovered previously unrecognized routes of vertical and sexual transmission. Here we describe inhibition of ZIKV replication by suramin, originally an anti-parasitic drug, which was more recently shown to inhibit multiple viruses. In cell culture-based assays, using reduction of cytopathic effect as read-out, suramin had an EC of ∼40 µM and a selectivity index of 48. In single replication cycle experiments, suramin treatment also caused a strong dose-dependent decrease in intracellular ZIKV RNA levels and a >3-log reduction in infectious progeny titers. Time-of-addition experiments revealed that suramin inhibits a very early step of the replication cycle as well as the release of infectious progeny. Only during the first 2 h of infection suramin treatment strongly reduced the fraction of cells that became infected with ZIKV, suggesting the drug affects virus binding/entry. Binding experiments at 4 °C using S-labeled ZIKV demonstrated that suramin interferes with attachment to host cells. When suramin treatment was initiated post-entry, viral RNA synthesis was unaffected, while both the release of genomes and the infectivity of ZIKV were reduced. This suggests the compound also affects virion biogenesis, possibly by interfering with glycosylation and the maturation of ZIKV during its traffic through the secretory pathway. The inhibitory effect of suramin on ZIKV attachment and virion biogenesis and its broad-spectrum activity warrant further evaluation of this compound as a potential therapeutic.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Vírion/efeitos dos fármacos
Ligação Viral/efeitos dos fármacos
Liberação de Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Efeito Citopatogênico Viral/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Flavivirus/efeitos dos fármacos
Glicosilação/efeitos dos fármacos
Ácido Micofenólico/administração & dosagem
Ácido Micofenólico/antagonistas & inibidores
RNA Viral/análise
RNA Viral/biossíntese
RNA Viral/efeitos dos fármacos
Suramina/administração & dosagem
Fatores de Tempo
Células Vero
Internalização do Vírus/efeitos dos fármacos
Zika virus/crescimento & desenvolvimento
Zika virus/fisiologia
Infecção pelo Zika virus/tratamento farmacológico
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Viral); 6032D45BEM (Suramin); HU9DX48N0T (Mycophenolic Acid)
[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:170503
[St] Status:MEDLINE


  2 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29074234
[Au] Autor:Sasaki M; Anindita PD; Phongphaew W; Carr M; Kobayashi S; Orba Y; Sawa H
[Ad] Endereço:Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
[Ti] Título:Development of a rapid and quantitative method for the analysis of viral entry and release using a NanoLuc luciferase complementation assay.
[So] Source:Virus Res;243:69-74, 2018 01 02.
[Is] ISSN:1872-7492
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Subviral particles (SVPs) self-assemble and are released from cells transfected with expression plasmids encoding flavivirus structural proteins. Flavivirus-like particles (VLPs), consisting of flavivirus structural proteins and a subgenomic replicon, can enter cells and cause single-round infections. Neither SVPs or VLPs possess complete viral RNA genomes, therefore are replication-incompetent systems; however, they retain the capacity to fuse and bud from target cells and follow the same maturation process as whole virions. SVPs and VLPs have been previously employed in studies analyzing entry and release steps of viral life cycles. In this study, we have developed quantitative methods for the detection of cellular entry and release of SVPs and VLPs by applying a luciferase complementation assay based on the high affinity interaction between the split NanoLuc luciferase protein, LgBiT and the small peptide, HiBiT. We introduced HiBiT into the structural protein of West Nile virus and generated SVPs and VLPs harboring HiBiT (SVP-HiBiT and VLP-HiBiT, respectively). As SVP-HiBiT emitted strong luminescence upon exposure to LgBiT and its substrate, the nascently budded SVP-HiBiT in the supernatant was readily quantified by luminometry. Similarly, the cellular entry of VLP-HiBiT generated luminescence when VLP-HiBiT was infected into LgBiT-expressing cells. These methods utilizing SVP-HiBiT and VLP-HiBiT will facilitate research into life cycles of flaviviruses, including WNV.
[Mh] Termos MeSH primário: Luciferases/análise
Vírion/fisiologia
Virologia/métodos
Internalização do Vírus
Liberação de Vírus
Vírus do Nilo Ocidental/fisiologia
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Luciferases/genética
Luciferases/metabolismo
Vírion/genética
Febre do Nilo Ocidental/virologia
Vírus do Nilo Ocidental/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171028
[St] Status:MEDLINE


  3 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28949903
[Au] Autor:Sonntag E; Milbradt J; Svrlanska A; Strojan H; Häge S; Kraut A; Hesse AM; Amin B; Sonnewald U; Couté Y; Marschall M
[Ad] Endereço:1​Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), Erlangen, Germany.
[Ti] Título:Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus.
[So] Source:J Gen Virol;98(10):2569-2581, 2017 Oct.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nuclear egress of herpesvirus capsids is mediated by a multi-component nuclear egress complex (NEC) assembled by a heterodimer of two essential viral core egress proteins. In the case of human cytomegalovirus (HCMV), this core NEC is defined by the interaction between the membrane-anchored pUL50 and its nuclear cofactor, pUL53. NEC protein phosphorylation is considered to be an important regulatory step, so this study focused on the respective role of viral and cellular protein kinases. Multiply phosphorylated pUL50 varieties were detected by Western blot and Phos-tag analyses as resulting from both viral and cellular kinase activities. In vitro kinase analyses demonstrated that pUL50 is a substrate of both PKCα and CDK1, while pUL53 can also be moderately phosphorylated by CDK1. The use of kinase inhibitors further illustrated the importance of distinct kinases for core NEC phosphorylation. Importantly, mass spectrometry-based proteomic analyses identified five major and nine minor sites of pUL50 phosphorylation. The functional relevance of core NEC phosphorylation was confirmed by various experimental settings, including kinase knock-down/knock-out and confocal imaging, in which it was found that (i) HCMV core NEC proteins are not phosphorylated solely by viral pUL97, but also by cellular kinases; (ii) both PKC and CDK1 phosphorylation are detectable for pUL50; (iii) no impact of PKC phosphorylation on NEC functionality has been identified so far; (iv) nonetheless, CDK1-specific phosphorylation appears to be required for functional core NEC interaction. In summary, our findings provide the first evidence that the HCMV core NEC is phosphorylated by cellular kinases, and that the complex pattern of NEC phosphorylation has functional relevance.
[Mh] Termos MeSH primário: Quinases Ciclina-Dependentes/metabolismo
Citomegalovirus/metabolismo
Proteína Quinase C-alfa/metabolismo
Proteínas Virais/metabolismo
Liberação de Vírus/fisiologia
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Proteína Quinase CDC2
Núcleo Celular/metabolismo
Quinases Ciclina-Dependentes/antagonistas & inibidores
Seres Humanos
Espectrometria de Massas
Fosforilação
Proteína Quinase C-alfa/antagonistas & inibidores
Proteína Quinase C-alfa/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Proteins); 0 (pUL50 protein, cytomegalovirus); 0 (pUL53 protein, cytomegalovirus); 0 (pUL97 protein, cytomegalovirus); EC 2.7.11.13 (PRKCA protein, human); EC 2.7.11.13 (Protein Kinase C-alpha); EC 2.7.11.22 (CDC2 Protein Kinase); EC 2.7.11.22 (CDK1 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000931


  4 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28878075
[Au] Autor:Nagashima S; Takahashi M; Kobayashi T; Nishizawa T; Nishiyama T; Primadharsini PP; Okamoto H; Tanggis
[Ad] Endereço:Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan.
[Ti] Título:Characterization of the Quasi-Enveloped Hepatitis E Virus Particles Released by the Cellular Exosomal Pathway.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our previous studies demonstrated that membrane-associated hepatitis E virus (HEV) particles-now considered "quasi-enveloped particles"-are present in the multivesicular body with intraluminal vesicles (exosomes) in infected cells and that the release of HEV virions is related to the exosomal pathway. In this study, we characterized exosomes purified from the culture supernatants of HEV-infected PLC/PRF/5 cells. Purified CD63-, CD9-, or CD81-positive exosomes derived from the culture supernatants of HEV-infected cells that had been cultivated in serum-free medium were found to contain HEV RNA and the viral capsid (ORF2) and ORF3 proteins, as determined by reverse transcription-PCR (RT-PCR) and Western blotting, respectively. Furthermore, immunoelectron microscopy, with or without prior detergent and protease treatment, revealed the presence of virus-like particles in the exosome fraction. These particles were 39.6 ± 1.0 nm in diameter and were covered with a lipid membrane. After treatment with detergent and protease, the diameter of these virus-like particles was 26.9 ± 0.9 nm, and the treated particles became accessible with an anti-HEV ORF2 monoclonal antibody (MAb). The HEV particles in the exosome fraction were capable of infecting naive PLC/PRF/5 cells but were not neutralized by an anti-HEV ORF2 MAb which efficiently neutralizes nonenveloped HEV particles in cell culture. These results indicate that the membrane-wrapped HEV particles released by the exosomal pathway are copurified with the exosomes in the exosome fraction and suggest that the capsids of HEV particles are individually covered by lipid membranes resembling those of exosomes, similar to enveloped viruses. Hepatitis E, caused by HEV, is an important infectious disease that is spreading worldwide. HEV infection can cause acute or fulminant hepatitis and can become chronic in immunocompromised hosts, including patients after organ transplantation. The HEV particles present in feces and bile are nonenveloped, while those in circulating blood and culture supernatants are covered with a cellular membrane, similar to enveloped viruses. Furthermore, these membrane-associated and -unassociated HEV particles can be propagated in cultured cells. The significance of our research is that the capsids of HEV particles are individually covered by a lipid membrane that resembles the membrane of exosomes, similar to enveloped viruses, and are released from infected cells via the exosomal pathway. These data will help to elucidate the entry mechanisms and receptors for HEV infection in the future. This is the first report to characterize the detailed morphological features of membrane-associated HEV particles.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/metabolismo
Exossomos/virologia
Vírus da Hepatite E/metabolismo
Hepatite E/metabolismo
Liberação de Vírus/fisiologia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais Murinos/farmacologia
Linhagem Celular
Exossomos/metabolismo
Anticorpos Anti-Hepatite/farmacologia
Seres Humanos
Liberação de Vírus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Murine-Derived); 0 (Capsid Proteins); 0 (Hepatitis Antibodies)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE


  5 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28794043
[Au] Autor:Brahms A; Mudhasani R; Pinkham C; Kota K; Nasar F; Zamani R; Bavari S; Kehn-Hall K
[Ad] Endereço:National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA.
[Ti] Título:Sorafenib Impedes Rift Valley Fever Virus Egress by Inhibiting Valosin-Containing Protein Function in the Cellular Secretory Pathway.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is an urgent need for therapeutic development to combat infections caused by Rift Valley fever virus (RVFV), which causes devastating disease in both humans and animals. In an effort to repurpose drugs for RVFV treatment, our previous studies screened a library of FDA-approved drugs. The most promising candidate identified was the hepatocellular and renal cell carcinoma drug sorafenib. Mechanism-of-action studies indicated that sorafenib targeted a late stage in virus infection and caused a buildup of virions within cells. In addition, small interfering RNA (siRNA) knockdown studies suggested that nonclassical targets of sorafenib are important for the propagation of RVFV. Here we extend our previous findings to identify the mechanism by which sorafenib inhibits the release of RVFV virions from the cell. Confocal microscopy imaging revealed that glycoprotein Gn colocalizes and accumulates within the endoplasmic reticulum (ER) and the transport of Gn from the Golgi complex to the host cell membrane is reduced. Transmission electron microscopy demonstrated that sorafenib caused virions to be present inside large vacuoles inside the cells. p97/valosin-containing protein (VCP), which is involved in membrane remodeling in the secretory pathway and a known target of sorafenib, was found to be important for RVFV egress. Knockdown of VCP resulted in decreased RVFV replication, reduced Gn Golgi complex localization, and increased Gn ER accumulation. The intracellular accumulation of RVFV virions was also observed in cells transfected with siRNA targeting VCP. Collectively, these data indicate that sorafenib causes a disruption in viral egress by targeting VCP and the secretory pathway, resulting in a buildup of virions within dilated ER vesicles. In humans, symptoms of RVFV infection mainly include a self-limiting febrile illness. However, in some cases, infected individuals can also experience hemorrhagic fever, neurological disorders, liver failure, and blindness, which could collectively be lethal. The ability of RVFV to expand geographically outside sub-Saharan Africa is of concern, particularly to the Americas, where native mosquito species are capable of virus transmission. Currently, there are no FDA-approved therapeutics to treat RVFV infection, and thus, there is an urgent need to understand the mechanisms by which the virus hijacks the host cell machinery to replicate. The significance of our research is in identifying the cellular target of sorafenib that inhibits RVFV propagation, so that this information can be used as a tool for the further development of therapeutics used to treat RVFV infection.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Proteínas de Ciclo Celular/metabolismo
Niacinamida/análogos & derivados
Compostos de Fenilureia/farmacologia
Febre do Vale de Rift/tratamento farmacológico
Vírus da Febre do Vale do Rift/fisiologia
Via Secretória/efeitos dos fármacos
Liberação de Vírus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Animais
Carcinoma Hepatocelular/tratamento farmacológico
Carcinoma Hepatocelular/metabolismo
Carcinoma Hepatocelular/virologia
Proteínas de Ciclo Celular/genética
Cercopithecus aethiops
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/virologia
Niacinamida/farmacologia
Febre do Vale de Rift/metabolismo
Febre do Vale de Rift/virologia
Vírus da Febre do Vale do Rift/efeitos dos fármacos
Células Tumorais Cultivadas
Proteína com Valosina
Células Vero
Vírion/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Phenylurea Compounds); 25X51I8RD4 (Niacinamide); 9ZOQ3TZI87 (sorafenib); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.4.6 (VCP protein, human); EC 3.6.4.6 (Valosin Containing Protein)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE


  6 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28779494
[Au] Autor:Ozcan KA; Berndsen CE
[Ad] Endereço:Department of Chemistry and Biochemistry, James Madison University, Harrisonburg, Virginia.
[Ti] Título:Bending of the BST-2 coiled-coil during viral budding.
[So] Source:Proteins;85(11):2081-2087, 2017 Nov.
[Is] ISSN:1097-0134
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BST-2/tetherin is a human extracellular transmembrane protein that serves as a host defense factor against HIV-1 and other viruses by inhibiting viral spreading. Structurally, BST-2 is a homo-dimeric coiled-coil that is connected to the host cell membrane by N and C terminal transmembrane anchors. The C-terminal membrane anchor of BST-2 is inserted into the budding virus while the N-terminal membrane anchor remains in the host cell membrane creating a viral tether. The structural mechanism of viral budding and tethering as mediated by BST-2 is not clear. To more fully describe the mechanism of viral tethering, we created a model of BST-2 embedded in a membrane and used steered molecular dynamics to simulate the transition from the host cell membrane associated form to the cell-virus membrane bridging form. We observed that BST-2 did not transition as a rigid structure, but instead bent at positions with a reduced interface between the helices of the coiled-coil. The simulations for the human BST-2 were then compared with simulations on the mouse homolog, which has no apparent weak spots. We observed that the mouse homolog spread the bending across the ectodomain, rather than breaking at discrete points as observed with the human homolog. These simulations support previous biochemical and cellular work suggesting some flexibility in the coiled-coil is necessary for viral tethering, while also highlighting how subtle changes in protein sequence can influence the dynamics and stability of proteins with overall similar structure.
[Mh] Termos MeSH primário: Antígenos CD/química
Antígenos CD/metabolismo
Modelos Biológicos
Simulação de Dinâmica Molecular
[Mh] Termos MeSH secundário: Animais
Proteínas Ligadas por GPI/química
Proteínas Ligadas por GPI/metabolismo
Seres Humanos
Camundongos
Fosfatidiletanolaminas
Maleabilidade
Liberação de Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (BST2 protein, human); 0 (GPI-Linked Proteins); 0 (Phosphatidylethanolamines)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE
[do] DOI:10.1002/prot.25362


  7 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28771128
[Au] Autor:Pourcel C; Midoux C; Vergnaud G; Latino L
[Ad] Endereço:Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
[Ti] Título:A carrier state is established in Pseudomonas aeruginosa by phage LeviOr01, a newly isolated ssRNA levivirus.
[So] Source:J Gen Virol;98(8):2181-2189, 2017 Aug.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:ssRNA bacteriophages are very abundant but poorly studied, particularly in relation to their effect on bacterial evolution. We isolated a new Pseudomonas aeruginosa levivirus, vB_PaeL_PcyII-10_LeviOr01, from hospital waste water. Its genome comprises 3669 nucleotides and encodes four putative proteins. Following bacterial infection, a carrier state is established in a fraction of the cells, conferring superinfection immunity. Such cells also resist other phages that use type IV pili as a receptor. The carrier population is composed of a mixture of cells producing phage, and susceptible cells that are non-carriers. Carrier cells accumulate phage until they burst, releasing large quantities of virions. The continuous presence of phage favours the emergence of host variants bearing mutations in genes involved in type IV pilus biogenesis, but also in genes affecting lipopolysaccharide (LPS) synthesis. The establishment of a carrier state in which phage particles are continuously released was previously reported for some dsRNA phages, but has not previously been described for a levivirus. The present results highlight the importance of the carrier state, an association that benefits both phages and bacteria and plays a role in bacterial evolution.
[Mh] Termos MeSH primário: Interações Hospedeiro-Parasita
Levivirus/fisiologia
Fagos de Pseudomonas/fisiologia
Pseudomonas aeruginosa/virologia
[Mh] Termos MeSH secundário: Genoma Viral
Levivirus/isolamento & purificação
Fagos de Pseudomonas/isolamento & purificação
RNA Viral/genética
Análise de Sequência de DNA
Liberação de Vírus
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000883


  8 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28768865
[Au] Autor:Han Z; Sagum CA; Takizawa F; Ruthel G; Berry CT; Kong J; Sunyer JO; Freedman BD; Bedford MT; Sidhu SS; Sudol M; Harty RN
[Ad] Endereço:Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate Egress.
[So] Source:J Virol;91(20), 2017 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ebola virus (EBOV) is a member of the family and the cause of hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main driving force for virion assembly and budding. Indeed, expression of eVP40 alone in mammalian cells results in the formation and budding of virus-like particles (VLPs) which mimic the budding process and morphology of authentic, infectious EBOV. To complete the budding process, eVP40 utilizes its PPXY L-domain motif to recruit a specific subset of host proteins containing one or more modular WW domains that then function to facilitate efficient production and release of eVP40 VLPs. In this report, we identified additional host WW-domain interactors by screening for potential interactions between mammalian proteins possessing one or more WW domains and WT or PPXY mutant peptides of eVP40. We identified the HECT family E3 ubiquitin ligase WWP1 and all four of its WW domains as strong interactors with the PPXY motif of eVP40. The eVP40-WWP1 interaction was confirmed by both peptide pulldown and coimmunoprecipitation assays, which also demonstrated that modular WW domain 1 of WWP1 was most critical for binding to eVP40. Importantly, the eVP40-WWP1 interaction was found to be biologically relevant for VLP budding since (i) small interfering RNA (siRNA) knockdown of endogenous WWP1 resulted in inhibition of eVP40 VLP egress, (ii) coexpression of WWP1 and eVP40 resulted in ubiquitination of eVP40 and a subsequent increase in eVP40 VLP egress, and (iii) an enzymatically inactive mutant of WWP1 (C890A) did not ubiquitinate eVP40 or enhance eVP40 VLP egress. Last, our data show that ubiquitination of eVP40 by WWP1 enhances egress of VLPs and concomitantly decreases cellular levels of higher-molecular-weight oligomers of eVP40. In sum, these findings contribute to our fundamental understanding of the functional interplay between host E3 ligases, ubiquitination, and regulation of EBOV VP40-mediated egress. Ebola virus (EBOV) is a high-priority, emerging human pathogen that can cause severe outbreaks of hemorrhagic fever with high mortality rates. As there are currently no approved vaccines or treatments for EBOV, a better understanding of the biology and functions of EBOV-host interactions that promote or inhibit viral budding is warranted. Here, we describe a physical and functional interaction between EBOV VP40 (eVP40) and WWP1, a host E3 ubiquitin ligase that ubiquitinates VP40 and regulates VLP egress. This viral PPXY-host WW domain-mediated interaction represents a potential new target for host-oriented inhibitors of EBOV egress.
[Mh] Termos MeSH primário: Ebolavirus/fisiologia
Interações Hospedeiro-Patógeno
Nucleoproteínas/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
Proteínas do Core Viral/metabolismo
Liberação de Vírus
[Mh] Termos MeSH secundário: Células HEK293
Seres Humanos
Nucleoproteínas/química
Nucleoproteínas/genética
RNA Interferente Pequeno
Ubiquitina-Proteína Ligases/genética
Ubiquitinação
Proteínas do Core Viral/química
Proteínas do Core Viral/genética
Proteínas da Matriz Viral/metabolismo
Vírion/fisiologia
Montagem de Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nucleoproteins); 0 (RNA, Small Interfering); 0 (Viral Core Proteins); 0 (Viral Matrix Proteins); 0 (nucleoprotein VP40, Ebola virus); EC 2.3.2.26 (WWP1 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE


  9 / 852 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28735115
[Au] Autor:Cui X; Yaghmaiean H; Wu G; Wu X; Chen X; Thorn G; Wang A
[Ad] Endereço:Institute of Vegetable Crops, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu 210014, China; London Research and Development Centre, Agriculture and Agri-Food Canada, London, Ontario N5V 4T3, Canada; Department of Biology, Western University, London, Ontario N6A 5B7, Canada.
[Ti] Título:The C-terminal region of the Turnip mosaic virus P3 protein is essential for viral infection via targeting P3 to the viral replication complex.
[So] Source:Virology;510:147-155, 2017 Oct.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Like other positive-strand RNA viruses, plant potyviruses assemble viral replication complexes (VRCs) on modified cellular membranes. Potyviruses encode two membrane proteins, 6K2 and P3. The former is known to play pivotal roles in the formation of membrane-associated VRCs. However, P3 remains to be one of the least characterized potyviral proteins. The P3 cistron codes for P3 as well as P3N-PIPO which results from RNA polymerase slippage. In this study, we show that the P3N-PIPO of Turnip mosaic virus (TuMV) is required for viral cell-to-cell movement but not for viral replication. We demonstrate that the C-terminal region of P3 (P3C) is indispensable for P3 to form cytoplasmic punctate inclusions and target VRCs. We reveal that TuMV mutants that lack P3C are replication-defective. Taken together, these data suggest that the P3 cistron has two distinct functions: P3N-PIPO as a dedicated movement protein and P3 as an essential component of the VRC.
[Mh] Termos MeSH primário: Proteínas de Membrana/metabolismo
Potyvirus/fisiologia
Proteínas Virais/metabolismo
Liberação de Vírus
Replicação Viral
[Mh] Termos MeSH secundário: Análise Mutacional de DNA
Proteínas de Membrana/genética
Proteínas do Movimento Viral em Plantas/genética
Proteínas do Movimento Viral em Plantas/metabolismo
Tabaco
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (Plant Viral Movement Proteins); 0 (Viral Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE


  10 / 852 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28724767
[Au] Autor:Klupp BG; Hellberg T; Granzow H; Franzke K; Dominguez Gonzalez B; Goodchild RE; Mettenleiter TC
[Ad] Endereço:Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
[Ti] Título:Integrity of the Linker of Nucleoskeleton and Cytoskeleton Is Required for Efficient Herpesvirus Nuclear Egress.
[So] Source:J Virol;91(19), 2017 Oct 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here that dominant negative SUN2 interferes with efficient herpesvirus nuclear egress, apparently by interfering with fusion between the primary virion envelope and outer nuclear membrane. This identifies a new cellular component important for viral egress and implicates LINC complex integrity in nonconventional nuclear membrane trafficking.
[Mh] Termos MeSH primário: Transporte Ativo do Núcleo Celular/fisiologia
Citoesqueleto/metabolismo
Herpesviridae/crescimento & desenvolvimento
Membrana Nuclear/metabolismo
Matriz Nuclear/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/genética
Animais
Linhagem Celular
Herpesviridae/metabolismo
Proteínas de Membrana/genética
Proteínas Associadas aos Microtúbulos/genética
Proteínas Nucleares/metabolismo
Coelhos
Suínos
Montagem de Vírus/fisiologia
Liberação de Vírus/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (Microtubule-Associated Proteins); 0 (Nuclear Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE



página 1 de 86 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde