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  1 / 9049 MEDLINE  
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[PMID]:28467896
[Au] Autor:Postigo A; Ramsden AE; Howell M; Way M
[Ad] Endereço:Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK.
[Ti] Título:Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication.
[So] Source:Cell Rep;19(5):1022-1032, 2017 May 02.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.
[Mh] Termos MeSH primário: Genoma Viral
Interações Hospedeiro-Patógeno
Vírus Vaccinia/fisiologia
Replicação Viral
[Mh] Termos MeSH secundário: Animais
Proteínas Mutadas de Ataxia Telangiectasia/genética
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Proteínas de Transporte/metabolismo
Linhagem Celular
Cercopithecus aethiops
Quinase do Ponto de Checagem 1/metabolismo
Proteínas de Ligação a DNA/metabolismo
Células HeLa
Seres Humanos
Proteínas Nucleares/metabolismo
Antígeno Nuclear de Célula em Proliferação/metabolismo
Proteína de Replicação A/metabolismo
Vírus Vaccinia/genética
Vírus Vaccinia/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (DNA-Binding Proteins); 0 (Nuclear Proteins); 0 (Proliferating Cell Nuclear Antigen); 0 (Replication Protein A); 0 (TOPBP1 protein, human); EC 2.7.11.1 (ATR protein, human); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.1 (CHEK1 protein, human); EC 2.7.11.1 (Checkpoint Kinase 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  2 / 9049 MEDLINE  
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[PMID]:29323851
[Au] Autor:Borisevich SV; Marennikova SS; Stovba LF; Petrov AA; Krotvov VT; Makhlai AA
[Ti] Título:Buffalopox.
[So] Source:Vopr Virusol;61(5):200-4, 2016.
[Is] ISSN:0507-4088
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:Buffalopox is a contagious viral disease affecting milch buffaloes (Bubalus Bubalis) and, rarely, cows. The disease has zoonotic implications, as outbreaks are frequently associated with human infections, particularly in the milkers. Buffalopox is associated with high morbidity (80%). The clinical symptoms of the disease are characterized by wartline lesions on the udder, teats, inguinal region, base of the ears, and over the parotid. In the severe form, generalized rash is observed. Although the disease does not lead to high mortality, it has an adverse effect on the productivity and working capacity of the animals resulting in large economic losses. The outbreaks of buffalopox occurred frequently in India, Pakistan, Bangladesh, Nepal, Iran, Egypt, and Indonesia, where buffaloes are reared as milch animals. The buffalopox is closely related with other Orthopoxviruses. In particular, it is close to the vaccinia virus. There is a view that the buffalopox virus might be derived from the vaccinia virus. It is possible that it became pathogenic to humans and animals through adaptive evolution of the genome by obtaining the virulence genes. PCR is performed for the C18L gene for the purpose of specific detection and differentiation of the buffalopox virus from other orthopoxviruses. The C18L gene encodes the ankyrin repeat protein, which determines the virus host range. The open reading frame of this gene is only 150-nucleotide long as against 453 nucleotide in the vaccinia virus, 756 - in the camelpox virus, and 759 - in the cowpox virus. It can be concluded that a systematic study based on the epidemiology of the virus, existence of reservoirs, biological transmission, and the molecular organization of the buffalopox virus from buffalo, cow, and humans may pave the way to a better understanding of the circulating virus and contribute to the control of the disease using the suitable diagnostic and prophylactic measures.
[Mh] Termos MeSH primário: Vírus da Varíola Bovina/genética
Varíola Bovina/epidemiologia
Surtos de Doenças
Vírus Vaccinia/genética
Vaccinia/veterinária
Zoonoses/epidemiologia
[Mh] Termos MeSH secundário: Animais
Repetição de Anquirina
Ásia Ocidental/epidemiologia
Búfalos/virologia
Bovinos
Varíola Bovina/transmissão
Varíola Bovina/virologia
Vírus da Varíola Bovina/classificação
Vírus da Varíola Bovina/isolamento & purificação
DNA Viral/genética
Oriente Médio/epidemiologia
Filogenia
Vaccinia/epidemiologia
Vaccinia/transmissão
Vaccinia/virologia
Vírus Vaccinia/classificação
Vírus Vaccinia/isolamento & purificação
Proteínas Virais/genética
Zoonoses/transmissão
Zoonoses/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Viral Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


  3 / 9049 MEDLINE  
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[PMID]:28989096
[Au] Autor:Wussow F; Chiuppesi F; Meng Z; Martinez J; Nguyen J; Barry PA; Diamond DJ
[Ad] Endereço:Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA, USA. Electronic address: fwussow@coh.org.
[Ti] Título:Exploiting 2A peptides to elicit potent neutralizing antibodies by a multi-subunit herpesvirus glycoprotein complex.
[So] Source:J Virol Methods;251:30-37, 2018 Jan.
[Is] ISSN:1879-0984
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Neutralizing antibodies (NAb) interfering with glycoprotein complex-mediated virus entry into host cells are thought to contribute to the protection against herpesvirus infection. However, using herpesvirus glycoprotein complexes as vaccine antigens can be complicated by the necessity of expressing multiple subunits simultaneously to allow efficient complex assembly and formation of conformational NAb epitopes. By using a novel bacterial artificial chromosome (BAC) clone of the clinically deployable Modified Vaccinia Ankara (MVA) vector and exploiting ribosomal skipping mediated by 2A peptides, MVA vectors were generated that expressed self-processing subunits of the human cytomegalovirus (HCMV) pentamer complex (PC) composed of gH, gL, UL128, UL130, and UL131A. These MVA vectors expressed 2A-linked HCMV PC subunits that were efficiently cleaved and transported to the cell surface as protein complexes forming conformational neutralizing epitopes. In addition, vaccination of mice by only two immunizations with these MVA vectors resulted in potent HCMV NAb responses that remained stable over a period of at least six months. This method of eliciting NAb by 2A-linked, self-processing HCMV PC subunits could contribute to develop a HCMV vaccine candidate and may serve as a template to facilitate the development of subunit vaccine strategies against other herpesviruses.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Antígenos Virais/imunologia
Vacinas contra Citomegalovirus/imunologia
Citomegalovirus/imunologia
Glicoproteínas/imunologia
Proteínas Estruturais Virais/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos Virais/genética
Citomegalovirus/genética
Vacinas contra Citomegalovirus/administração & dosagem
Vacinas contra Citomegalovirus/genética
Vetores Genéticos
Glicoproteínas/genética
Esquemas de Imunização
Camundongos
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Vírus Vaccinia/genética
Proteínas Estruturais Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Cytomegalovirus Vaccines); 0 (Glycoproteins); 0 (Vaccines, Synthetic); 0 (Viral Structural Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171010
[St] Status:MEDLINE


  4 / 9049 MEDLINE  
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[PMID]:28987424
[Au] Autor:Barbieri A; Panigada M; Soprana E; Di Mario G; Gubinelli F; Bernasconi V; Recagni M; Donatelli I; Castrucci MR; Siccardi AG
[Ad] Endereço:Molecular Immunology Unit, San Raffaele Research Institute, Via Olgettina 58, 20132, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli, 32, 20129, Milan, Italy.
[Ti] Título:Strategies to obtain multiple recombinant modified vaccinia Ankara vectors. Applications to influenza vaccines.
[So] Source:J Virol Methods;251:7-14, 2018 Jan.
[Is] ISSN:1879-0984
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI. Exploiting this strategy, both double and triple rMVA were constructed, expressing as transgenes the influenza A proteins HA, NP, M1, and PB1. Upon validation of the harbored transgenes co-expression, double and triple recombinants rMVA(ΔIII)-NP-P2A-M1 and rMVA(ΔIII)-NP-P2A-M1-(ΔVI)-PB1 were assayed for in vivo immunogenicity and protection against lethal challenge. In vivo responses were identical to those obtained with the reported combinations of single recombinants, supporting the feasibility and reliability of the present improvement and the extension of Red-to-Green gene swapping to insertion sites other than ΔIII.
[Mh] Termos MeSH primário: Portadores de Fármacos
Vetores Genéticos
Vacinas contra Influenza/imunologia
Vírus Vaccinia/genética
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Antígenos Virais/genética
Antígenos Virais/imunologia
Linfócitos T CD8-Positivos/imunologia
Expressão Gênica
Vacinas contra Influenza/administração & dosagem
Vacinas contra Influenza/genética
Camundongos Endogâmicos C57BL
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Análise de Sobrevida
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Proteínas Virais/genética
Proteínas Virais/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Drug Carriers); 0 (Influenza Vaccines); 0 (Recombinant Proteins); 0 (Vaccines, Synthetic); 0 (Viral Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


  5 / 9049 MEDLINE  
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[PMID]:28468973
[Au] Autor:Tian T; Jin MQ; Dubin K; King SL; Hoetzenecker W; Murphy GF; Chen CA; Kupper TS; Fuhlbrigge RC
[Ad] Endereço:Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; ttian@partners.org Robert.Fuhlbrigge@childrenscolorado.org.
[Ti] Título:IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection.
[So] Source:J Immunol;198(11):4341-4351, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1 ) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. The phenotype of infected IL-1R1 mice was similar to eczema vaccinatum, a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis. Interestingly, the impaired cutaneous response of IL-1R1 mice did not reflect a systemic immune deficiency, because immunized IL-1R1 mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of wild-type mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1 mice contained significantly more macrophages and monocyte-derived dendritic cells in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1 mice. These results suggest new therapeutic strategies for treatment of eczema vaccinatum and inform assessment of risks in patients receiving IL-1 blocking Abs for treatment of chronic inflammatory disorders.
[Mh] Termos MeSH primário: Proteína Antagonista do Receptor de Interleucina 1/deficiência
Proteína Antagonista do Receptor de Interleucina 1/imunologia
Dermatopatias Infecciosas/imunologia
Pele/patologia
Vírus Vaccinia/imunologia
Vaccinia/imunologia
[Mh] Termos MeSH secundário: Administração Cutânea
Animais
Linfócitos T CD8-Positivos/imunologia
Proteína Antagonista do Receptor de Interleucina 1/genética
Erupção Variceliforme de Kaposi/imunologia
Erupção Variceliforme de Kaposi/fisiopatologia
Erupção Variceliforme de Kaposi/terapia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Pele/anatomia & histologia
Pele/imunologia
Pele/virologia
Vacinação
Vírus Vaccinia/fisiologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Interleukin 1 Receptor Antagonist Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1500106


  6 / 9049 MEDLINE  
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[PMID]:29216299
[Au] Autor:Kim YG; Baltabekova AZ; Zhiyenbay EE; Aksambayeva AS; Shagyrova ZS; Khannanov R; Ramanculov EM; Shustov AV
[Ad] Endereço:National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.
[Ti] Título:Recombinant Vaccinia virus-coded interferon inhibitor B18R: Expression, refolding and a use in a mammalian expression system with a RNA-vector.
[So] Source:PLoS One;12(12):e0189308, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:B18R protein of Vaccinia virus binds to type I interferons and inhibits activation of interferon-mediated signal transduction. Cells which have unimpaired interferon signaling such as primary cell cultures or some industrially important cell lines are capable of development of an antiviral state. An establishment of the antiviral state limits replication of RNA-viruses and can suppress replication of RNA vectors. The interferon inhibitor B18R effectively prevents the establishment of the antiviral state. For this reason, B18R has become a ubiquitous component of protocols for epigenetic reprogramming which use transfections of RNA replicons or mRNA. Despite wide practical applicability, commercially available B18R is predominantly produced in cell cultures and little information has been published on a production and use of bacterially expressed B18R. Objectives of this study were to produce B18R in an E.coli expression system and to confirm the product's biological activity by using it to maintain RNA-vectors in cell cultures capable of the antiviral state. The described method allows the expression and efficient refolding to obtain 10-100 mg of B18R from a small-scale culture and the production process is economically attractive compared to a use of an eukaryotic expression. To check for a presence of the biological activity of bacterially-expressed B18R the protein was used to support persistence of an autonomously replicating RNA-vector in a cell culture which is capable of the antiviral state. A RNA-containing virus, Venezuelan equine encephalitis virus (VEE) can serve as an efficient vector for heterologous expression in cell cultures, although its replication is sensitive to the effects of type I interferons which limit a range of cell lines for a use with this vector. The VEE replicon was utilized to direct an expression of recombinant human granulocyte colony stimulating factor (G-CSF). The producing replicon could persist in HEK293 cells for sufficiently long time only in presence of B18R, whereas addition of B18R not only allowed persistence of the replicon but also increased production from the replicon. A model product granulocyte colony stimulating factor accumulated to 35.5 µg/ml during a 7 day experiment. This work describes efficacious expression and refolding of the viral cytokine inhibitor and demonstrates a utility of bacterially-expressed B18R.
[Mh] Termos MeSH primário: Vetores Genéticos
RNA Viral/genética
Vírus Vaccinia/genética
Proteínas Virais/genética
[Mh] Termos MeSH secundário: Cromatografia em Gel
Eletroforese em Gel de Poliacrilamida
Células HEK293
Seres Humanos
Dobramento de Proteína
Proteínas Recombinantes/genética
Proteínas Virais/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral); 0 (Recombinant Proteins); 0 (Viral Proteins); 135847-80-2 (B18R protein, Vaccinia virus)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189308


  7 / 9049 MEDLINE  
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[PMID]:28458036
[Au] Autor:Meador LR; Kessans SA; Kilbourne J; Kibler KV; Pantaleo G; Roderiguez ME; Blattman JN; Jacobs BL; Mor TS
[Ad] Endereço:Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ, USA; Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, USA.
[Ti] Título:A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.
[So] Source:Virology;507:242-256, 2017 07.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/administração & dosagem
Proteína gp41 do Envelope de HIV/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Imunização/métodos
Tabaco/metabolismo
Vírus Vaccinia/fisiologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/imunologia
Animais
Anticorpos Neutralizantes/imunologia
Formação de Anticorpos
Feminino
Vetores Genéticos/genética
Vetores Genéticos/fisiologia
Anticorpos Anti-HIV/imunologia
Proteína gp41 do Envelope de HIV/administração & dosagem
Proteína gp41 do Envelope de HIV/genética
Infecções por HIV/prevenção & controle
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Imunização Secundária
Camundongos
Camundongos Endogâmicos C57BL
Tabaco/genética
Tabaco/virologia
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
Vírus Vaccinia/genética
Replicação Viral
Produtos do Gene gag do Vírus da Imunodeficiência Humana/administração & dosagem
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp41); 0 (Vaccines, Virus-Like Particle); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  8 / 9049 MEDLINE  
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[PMID]:29077752
[Au] Autor:Baldanta S; Fernández-Escobar M; Acín-Perez R; Albert M; Camafeita E; Jorge I; Vázquez J; Enríquez JA; Guerra S
[Ad] Endereço:Department of Preventive Medicine, Public Health and Microbiology, Universidad Autónoma, Madrid, Spain.
[Ti] Título:ISG15 governs mitochondrial function in macrophages following vaccinia virus infection.
[So] Source:PLoS Pathog;13(10):e1006651, 2017 Oct.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS) were pathways altered in ISG15-/- BMDM treated with IFN. Mitochondrial respiration, Adenosine triphosphate (ATP) and reactive oxygen species (ROS) production was higher in ISG15+/+ BMDM than in ISG15-/- BMDM following IFN treatment, indicating the involvement of ISG15-dependent mechanisms. An additional consequence of ISG15 depletion was a significant change in macrophage polarization. Although infected ISG15-/- macrophages showed a robust proinflammatory cytokine expression pattern typical of an M1 phenotype, a clear blockade of nitric oxide (NO) production and arginase-1 activation was detected. Accordingly, following IFN treatment, NO release was higher in ISG15+/+ macrophages than in ISG15-/- macrophages concomitant with a decrease in viral titer. Thus, ISG15-/- macrophages were permissive for VACV replication following IFN treatment. In conclusion, our results demonstrate that ISG15 governs the dynamic functionality of mitochondria, specifically, OXPHOS and mitophagy, broadening its physiological role as an antiviral agent.
[Mh] Termos MeSH primário: Citocinas/metabolismo
Macrófagos/metabolismo
Mitocôndrias/metabolismo
Degradação Mitocondrial
Vírus Vaccinia/metabolismo
Vaccinia/metabolismo
[Mh] Termos MeSH secundário: Animais
Arginase/genética
Arginase/metabolismo
Citocinas/genética
Ativação Enzimática/genética
Macrófagos/patologia
Camundongos
Camundongos Knockout
Mitocôndrias/genética
Mitocôndrias/patologia
Óxido Nítrico/metabolismo
Fosforilação Oxidativa
Ubiquitinas/genética
Ubiquitinas/metabolismo
Vaccinia/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (G1p2 protein, mouse); 0 (Ubiquitins); 31C4KY9ESH (Nitric Oxide); EC 3.5.3.1 (Arg1 protein, mouse); EC 3.5.3.1 (Arginase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171028
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006651


  9 / 9049 MEDLINE  
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[PMID]:29020595
[Au] Autor:Schrick L; Tausch SH; Dabrowski PW; Damaso CR; Esparza J; Nitsche A
[Ad] Endereço:Robert Koch Institute, Berlin, Germany.
[Ti] Título:An Early American Smallpox Vaccine Based on Horsepox.
[So] Source:N Engl J Med;377(15):1491-1492, 2017 10 12.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Doenças dos Cavalos/virologia
Orthopoxvirus/genética
Vacina Antivariólica/história
Varíola/história
Vírus Vaccinia/genética
[Mh] Termos MeSH secundário: Animais
Genoma Viral
História do Século XIX
História do Século XX
Cavalos
Seres Humanos
Varíola/prevenção & controle
Varíola/veterinária
Varíola/virologia
Vírus Vaccinia/imunologia
[Pt] Tipo de publicação:HISTORICAL ARTICLE; LETTER; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Smallpox Vaccine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMc1707600


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[PMID]:29020058
[Au] Autor:McCurley NP; Domi A; Basu R; Saunders KO; LaBranche CC; Montefiori DC; Haynes BF; Robinson HL
[Ad] Endereço:GeoVax Inc., Smyrna, GA, United States of America.
[Ti] Título:HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
[So] Source:PLoS One;12(10):e0177863, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Neutralizantes/imunologia
Antígenos CD4/metabolismo
Infecções por HIV/imunologia
Infecções por HIV/transmissão
[Mh] Termos MeSH secundário: Animais
Formação de Anticorpos/imunologia
Sítios de Ligação
Feminino
Células HEK293
Antígenos HIV/imunologia
Seres Humanos
Macaca mulatta
Vacinas de DNA/imunologia
Vírus Vaccinia/imunologia
Vírus Vaccinia/ultraestrutura
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (HIV Antigens); 0 (Vaccines, DNA); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177863



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