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[PMID]:28714847
[Au] Autor:Pollock N; Taylor G; Jobe F; Guzman E
[Ad] Endereço:1​School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK 2​The Pirbright Institute, Ash Road, Pirbright, Woking, RG8 0JU, UK.
[Ti] Título:Modulation of the transcription factor NF-κB in antigen-presenting cells by bovine respiratory syncytial virus small hydrophobic protein.
[So] Source:J Gen Virol;98(7):1587-1599, 2017 Jul.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease in young cattle and is closely related to human RSV (HRSV), which causes severe respiratory disease in infants and the elderly. The RSV genome encodes a small hydrophobic (SH) protein with viroporin activity. Previous studies have shown that recombinant BRSV lacking the SH gene (rBRSVΔSH) is attenuated in the lungs, but not in the upper respiratory tract, of calves and mucosal vaccination with rBRSVΔSH induced long-lasting protective immunity. Attenuation of rBRSVΔSH may be due to the ability of this virus to induce an early innate response as rBRSVΔSH induces higher levels of pro-inflammatory cytokines than wild-type (wt) rBRSV. In this study, we investigated the effects of the BRSV SH protein on NF-κB p65 phosphorylation, a master step in the regulation of pro-inflammatory cytokines. Expression of SH resulted in the inhibition of NF-κB p65 phosphorylation in response to BRSV infection and extracellular lipopolysaccharide, and a reduction in the production of pro-inflammatory cytokines. In contrast, rBRSVΔSH does not inhibit NF-κB p65 phosphorylation in bovine antigen-presenting cells, including monocytes, macrophages and dendritic cells, resulting in increased expression of pro-inflammatory cytokines and increased activation of T cells compared to cells infected with wt BRSV. These findings highlight an important role for the BRSV SH protein in immune modulation.
[Mh] Termos MeSH primário: Citocinas/metabolismo
Células Dendríticas/imunologia
Macrófagos/imunologia
Monócitos/imunologia
Vírus Sincicial Respiratório Bovino/metabolismo
Proteínas Oncogênicas de Retroviridae/imunologia
Fator de Transcrição RelA/metabolismo
[Mh] Termos MeSH secundário: Animais
Bovinos
Doenças dos Bovinos/imunologia
Doenças dos Bovinos/virologia
Linhagem Celular
Células Dendríticas/metabolismo
Células Dendríticas/virologia
Seres Humanos
Lipopolissacarídeos/metabolismo
Ativação Linfocitária/imunologia
Macrófagos/metabolismo
Macrófagos/virologia
Camundongos
Monócitos/metabolismo
Monócitos/virologia
Inibidor de NF-kappaB alfa/metabolismo
Fosforilação
Células RAW 264.7
Vírus Sincicial Respiratório Bovino/genética
Vírus Sincicial Respiratório Bovino/imunologia
Proteínas Oncogênicas de Retroviridae/genética
Proteínas Oncogênicas de Retroviridae/metabolismo
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Lipopolysaccharides); 0 (Retroviridae Proteins, Oncogenic); 0 (Transcription Factor RelA); 0 (small hydrophobic protein, virus); 139874-52-5 (NF-KappaB Inhibitor alpha)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000855


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[PMID]:27287400
[Au] Autor:Moidunny S; Matos M; Wesseling E; Banerjee S; Volsky DJ; Cunha RA; Agostinho P; Boddeke HW; Roy S
[Ad] Endereço:Department of Surgery, Division of Basic and Translational Research, University of Minnesota, Minneapolis, MN, USA.
[Ti] Título:Oncostatin M promotes excitotoxicity by inhibiting glutamate uptake in astrocytes: implications in HIV-associated neurotoxicity.
[So] Source:J Neuroinflammation;13(1):144, 2016 Jun 10.
[Is] ISSN:1742-2094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Elevated levels of oncostatin M (OSM), an interleukin-6 cytokine family member, have been observed in HIV-1-associated neurocognitive disorders (HAND) and Alzheimer's disease. However, the function of OSM in these disease conditions is unclear. Since deficient glutamate uptake by astrocytes is instrumental in HAND-associated neurotoxicity, we hypothesized that OSM impairs glutamate uptake in astrocytes and thereby promotes neuronal excitotoxicity. METHODS: Primary cultures of mouse cortical astrocytes, neurons, microglia, and BV2 cell line were used. The expression of glutamate transporters (GLAST/EAAT1 and GLT-1/EAAT2) was investigated using real-time PCR and Western blot, and their activity was assessed by measuring (3)H-D-aspartate uptake. Neuronal toxicity was measured using the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl-) 2,5-diphenyltetrazolium bromide) assay and immunocytochemistry. A chimeric HIV-1 that infects murine cells (EcoHIV/NL4-3-GFP virus (EcoHIV)) was used to investigate whether the virus induces OSM, OSM receptor (OSMR)-ß, glycoprotein 130 (gp130), GLT-1, GLAST (mRNA and protein), and OSM release (ELISA) in cultured BV2 cells, primary microglia, or astrocytes. Statistical analyses of the data were performed using one-way ANOVA (to allow multiple comparisons) and two-tailed Student's t test. RESULTS: OSM treatment (10 ng/mL) time-dependently reduced GLAST and GLT-1 expression and inhibited (3)H-D-aspartate uptake in cultured astrocytes in a concentration-dependent manner, an effect prevented by the Janus kinase (JAK)/signal transducers and activators of transcription (STAT)3 inhibitor AG490. Down-regulation of astrocytic glutamate transport by OSM resulted in NMDA receptor-dependent excitotoxicity in cortical neurons. Infection with EcoHIV induced OSM gene expression and protein release in BV2 cells and microglia, but not in astrocytes. Conversely, EcoHIV caused a fivefold increase in OSMR-ß mRNA (but not gp130) and protein in astrocytes, but not in microglia, which did not express OSMR-ß protein. Finally, astrocytic expression of GLAST gene was unaffected by EcoHIV, whereas GLT-1 mRNA was increased by twofold. CONCLUSIONS: We provide first evidence that activation of JAK/STAT3 signaling by OSM inhibits glutamate uptake in astrocytes, which results in neuronal excitotoxicity. Our findings with EcoHIV suggest that targeting OSMR-ß signaling in astrocytes might alleviate HIV-1-associated excitotoxicity.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Astrócitos/efeitos dos fármacos
Astrócitos/metabolismo
Ácido Glutâmico/metabolismo
Oncostatina M/efeitos adversos
[Mh] Termos MeSH secundário: Sistema X-AG de Transporte de Aminoácidos/metabolismo
Animais
Antineoplásicos/farmacologia
Antineoplásicos/toxicidade
Ácido Aspártico/metabolismo
Astrócitos/virologia
Células Cultivadas
Córtex Cerebral/citologia
Citocinas/genética
Citocinas/metabolismo
Embrião de Mamíferos
Agonistas de Aminoácidos Excitatórios/toxicidade
Transportador 2 de Aminoácido Excitatório/metabolismo
Proteína Glial Fibrilar Ácida/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
N-Metilaspartato/toxicidade
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Oncostatina M/farmacologia
Subunidade beta de Receptor de Oncostatina M/metabolismo
Proteínas Oncogênicas de Retroviridae/toxicidade
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport System X-AG); 0 (Antineoplastic Agents); 0 (Cytokines); 0 (Excitatory Amino Acid Agonists); 0 (Excitatory Amino Acid Transporter 2); 0 (Glial Fibrillary Acidic Protein); 0 (Oncostatin M Receptor beta Subunit); 0 (Osmr protein, mouse); 0 (Retroviridae Proteins, Oncogenic); 0 (Slc1a2 protein, mouse); 0 (p24 protein, Human T-lymphotropic virus 1); 106956-32-5 (Oncostatin M); 30KYC7MIAI (Aspartic Acid); 3KX376GY7L (Glutamic Acid); 6384-92-5 (N-Methylaspartate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160612
[St] Status:MEDLINE
[do] DOI:10.1186/s12974-016-0613-8


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[PMID]:27235335
[Au] Autor:Amirnasr M; Fallah Tafti T; Sankian M; Rezaei A; Tafaghodi M
[Ad] Endereço:Student Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amirnasrm@yahoo.com.
[Ti] Título:Immunization against HTLV-I with chitosan and tri-methylchitosan nanoparticles loaded with recombinant env23 and env13 antigens of envelope protein gp46.
[So] Source:Microb Pathog;97:38-44, 2016 Aug.
[Is] ISSN:1096-1208
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To prevent the spread of HTLV-I (Human T-lymphotropic virus type 1), a safe and effective vaccine is required. To increase immune responses against the peptide antigens can be potentiated with polymer-based nanoparticles, like chitosan (CHT) and trimethylchitosan (TMC), as delivery system/adjuvant. CHT and TMC nanoparticles loaded with recombinant proteins (env23 & env13) of gp46 were prepared by direct coating of antigens with positively charged polymers. The size of CHT and TMC nanoparticles (NPs) loaded with each antigen was about 400 nm. The physical stability of NPs was followed for 4 weeks. Both formulations showed to be stable for about 15 days. The immunogenicity of NPs loaded with antigens was studied after nasal and subcutaneous immunization in mice. Three immunizations (7.5 µg antigen) were performed with 2 weeks intervals. Two weeks after the last booster dose, sera IgG subtypes were measured. After subcutaneous administration, for both nanoparticulate antigens, serum IgG1 and IgGtotal levels were higher than antigen solution (P < 0.001). After nasal administration, for env23, IgG2a levels and IgG2a/IgG1 ratio was significantly higher than groups with subcutaneous administration (P < 0.001). Both nanoparticles showed good immunoadjuvant potential. Env23 antigen was a better candidate for vaccination against HTLV-I, as it induced higher cellular immune responses, compared with env13.
[Mh] Termos MeSH primário: Antígenos Virais/imunologia
Quitosana/administração & dosagem
Produtos do Gene env/imunologia
Vírus 1 Linfotrópico T Humano/imunologia
Nanopartículas/administração & dosagem
Proteínas Oncogênicas de Retroviridae/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem
Administração Intranasal
Animais
Anticorpos Antivirais/sangue
Antígenos Virais/genética
Portadores de Fármacos/administração & dosagem
Estabilidade de Medicamentos
Produtos do Gene env/genética
Vírus 1 Linfotrópico T Humano/genética
Imunoglobulina G/sangue
Injeções Subcutâneas
Masculino
Camundongos Endogâmicos BALB C
Proteínas Oncogênicas de Retroviridae/genética
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Vacinas Virais/administração & dosagem
Vacinas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Drug Carriers); 0 (Gene Products, env); 0 (Immunoglobulin G); 0 (N-trimethyl chitosan chloride); 0 (Retroviridae Proteins, Oncogenic); 0 (Vaccines, Synthetic); 0 (Viral Vaccines); 0 (gp46 protein, Human T-cell leukemia virus type I); 9012-76-4 (Chitosan)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170327
[Lr] Data última revisão:
170327
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160529
[St] Status:MEDLINE


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[PMID]:27038378
[Au] Autor:To J; Surya W; Torres J
[Ad] Endereço:School of Biological Sciences, Nanyang Technological University, Singapore.
[Ti] Título:Targeting the Channel Activity of Viroporins.
[So] Source:Adv Protein Chem Struct Biol;104:307-355, 2016.
[Is] ISSN:1876-1623
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Since the discovery that certain small viral membrane proteins, collectively termed as viroporins, can permeabilize host cellular membranes and also behave as ion channels, attempts have been made to link this feature to specific biological roles. In parallel, most viroporins identified so far are virulence factors, and interest has focused toward the discovery of channel inhibitors that would have a therapeutic effect, or be used as research tools to understand the biological roles of viroporin ion channel activity. However, this paradigm is being shifted by the difficulties inherent to small viral membrane proteins, and by the realization that protein-protein interactions and other diverse roles in the virus life cycle may represent an equal, if not, more important target. Therefore, although targeting the channel activity of viroporins can probably be therapeutically useful in some cases, the focus may shift to their other functions in following years. Small-molecule inhibitors have been mostly developed against the influenza A M2 (IAV M2 or AM2). This is not surprising since AM2 is the best characterized viroporin to date, with a well-established biological role in viral pathogenesis combined the most extensive structural investigations conducted, and has emerged as a validated drug target. For other viroporins, these studies are still mostly in their infancy, and together with those for AM2, are the subject of the present review.
[Mh] Termos MeSH primário: Membrana Celular/metabolismo
Canais Iônicos/genética
Mapas de Interação de Proteínas
Proteínas do Envelope Viral/metabolismo
[Mh] Termos MeSH secundário: Membrana Celular/genética
Seres Humanos
Canais Iônicos/metabolismo
Proteínas Oncogênicas de Retroviridae/metabolismo
Proteínas da Matriz Viral/metabolismo
Proteínas não Estruturais Virais/metabolismo
Proteínas Virais/metabolismo
Proteínas Virais Reguladoras e Acessórias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (2B protein, poliovirus); 0 (Ion Channels); 0 (M2 protein, Influenza A virus); 0 (Retroviridae Proteins, Oncogenic); 0 (Viral Envelope Proteins); 0 (Viral Matrix Proteins); 0 (Viral Nonstructural Proteins); 0 (Viral Proteins); 0 (Viral Regulatory and Accessory Proteins); 0 (agnoprotein, polyomavirus); 0 (p7 protein, Hepatitis C virus); 0 (small hydrophobic protein, virus)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160403
[St] Status:MEDLINE


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[PMID]:26848684
[Au] Autor:Fujii H; Shimizu M; Miyagi T; Kunihiro M; Tanaka R; Takahashi Y; Tanaka Y
[Ad] Endereço:Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Okinawa 903-0215, Japan. hfujii@med.u-ryukyu.ac.jp.
[Ti] Título:A Potential of an Anti-HTLV-I gp46 Neutralizing Monoclonal Antibody (LAT-27) for Passive Immunization against Both Horizontal and Mother-to-Child Vertical Infection with Human T Cell Leukemia Virus Type-I.
[So] Source:Viruses;8(2), 2016 Feb 03.
[Is] ISSN:1999-4915
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Although the number of human T-cell leukemia virus type-I (HTLV-I)-infected individuals in the world has been estimated at over 10 million, no prophylaxis vaccines against HTLV-I infection are available. In this study, we took a new approach for establishing the basis of protective vaccines against HTLV-I. We show here the potential of a passively administered HTLV-I neutralizing monoclonal antibody of rat origin (LAT-27) that recognizes epitopes consisting of the HTLV-I gp46 amino acids 191-196. LAT-27 completely blocked HTLV-I infection in vitro at a minimum concentration of 5 µg/mL. Neonatal rats born to mother rats pre-infused with LAT-27 were shown to have acquired a large quantity of LAT-27, and these newborns showed complete resistance against intraperitoneal infection with HTLV-I. On the other hand, when humanized immunodeficient mice were pre-infused intravenously with humanized LAT-27 (hu-LAT-27), all the mice completely resisted HTLV-I infection. These results indicate that hu-LAT-27 may have a potential for passive immunization against both horizontal and mother-to-child vertical infection with HTLV-I.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Transmissão de Doença Infecciosa/prevenção & controle
Produtos do Gene env/imunologia
Infecções por HTLV-I/prevenção & controle
Infecções por HTLV-I/transmissão
Vírus 1 Linfotrópico T Humano/fisiologia
Transmissão Vertical de Doença Infecciosa/prevenção & controle
Proteínas Oncogênicas de Retroviridae/imunologia
[Mh] Termos MeSH secundário: Adulto
Animais
Anticorpos Monoclonais/administração & dosagem
Feminino
Produtos do Gene env/genética
Infecções por HTLV-I/imunologia
Infecções por HTLV-I/virologia
Vírus 1 Linfotrópico T Humano/genética
Vírus 1 Linfotrópico T Humano/imunologia
Seres Humanos
Imunização Passiva
Lactente
Masculino
Camundongos
Ratos
Ratos Endogâmicos F344
Ratos Sprague-Dawley
Proteínas Oncogênicas de Retroviridae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Gene Products, env); 0 (Retroviridae Proteins, Oncogenic); 0 (gp46 protein, Human T-cell leukemia virus type I)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160206
[St] Status:MEDLINE


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[PMID]:26486979
[Au] Autor:Hartmann K
[Ad] Endereço:Medizinische Kleintierklinik, Ludwig-Maximilians-Universität München, Veterinärstrasse 13, 80539 Munich, Germany vorstandsassistenz@medizinische-kleintierklinik.de.
[Ti] Título:Efficacy of antiviral chemotherapy for retrovirus-infected cats: What does the current literature tell us?
[So] Source:J Feline Med Surg;17(11):925-39, 2015 Nov.
[Is] ISSN:1532-2750
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:GLOBAL IMPORTANCE: The two feline retroviruses, feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), are global and widespread, but differ in their potential to cause disease. VIRAL INFECTION - FIV: FIV, a lentivirus that shares many properties with human immunodeficiency virus (HIV), can cause an acquired immune deficiency syndrome, which predisposes cats to other infections, stomatitis, neurological disorders and tumours. Although secondary infections are common, specific opportunistic infections or acquired immunodeficiency virus-defining infections, such as those that occur with HIV, are not commonly reported in FIV-infected cats. In most naturally infected cats, FIV does not cause a severe clinical syndrome; with appropriate care, FIV-infected cats can live many years before succumbing to conditions unrelated to their FIV infection. Thus, overall survival time is not necessarily shorter than in uninfected cats, and quality of life is usually high over many years or lifelong. VIRAL INFECTION - FELV: FeLV, an oncornavirus, is more pathogenic than FIV. Historically, it was considered to account for more disease-related deaths and clinical syndromes in cats than any other infectious agent. Recently, the prevalence and importance of FeLV have been decreasing, mainly because of testing and eradication programmes and the use of FeLV vaccines. Progressive FeLV infection can cause tumours, bone marrow suppression and immunosuppression, as well as neurological and other disorders, and leads to a decrease in life expectancy. However, with appropriate care, many FeLV-infected cats can also live several years with a good quality of life. PRACTICAL RELEVANCE: A decision regarding treatment or euthanasia should never be based solely on the presence or absence of a retrovirus infection. Antiviral chemotherapy is of increasing interest in veterinary medicine, but is still not used commonly. EVIDENCE BASE: This article reviews the current literature on antiviral chemotherapy in retrovirus-infected cats, focusing on drugs that are currently available on the market and, thus, could potentially be used in cats.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Síndrome de Imunodeficiência Adquirida Felina/tratamento farmacológico
Proteínas Oncogênicas de Retroviridae/uso terapêutico
Vacinação/veterinária
Vacinas Virais/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Gatos
Síndrome de Imunodeficiência Adquirida Felina/diagnóstico
Síndrome de Imunodeficiência Adquirida Felina/patologia
Vírus da Imunodeficiência Felina/isolamento & purificação
Guias de Prática Clínica como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Retroviridae Proteins, Oncogenic); 0 (Viral Vaccines); 0 (feline leukemia virus vaccine)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:151021
[Lr] Data última revisão:
151021
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151022
[St] Status:MEDLINE
[do] DOI:10.1177/1098612X15610676


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[PMID]:26459979
[Au] Autor:Westman ME; Malik R; Hall E; Sheehy PA; Norris JM
[Ad] Endereço:Faculty of Veterinary Science, The University of Sydney, NSW 2006, Australia. Electronic address: mark.westman@sydney.edu.au.
[Ti] Título:Determining the feline immunodeficiency virus (FIV) status of FIV-vaccinated cats using point-of-care antibody kits.
[So] Source:Comp Immunol Microbiol Infect Dis;42:43-52, 2015 Oct.
[Is] ISSN:1878-1667
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This study challenges the commonly held view that the feline immunodeficiency virus (FIV) infection status of FIV-vaccinated cats cannot be determined using point-of-care antibody test kits due to indistinguishable antibody production in FIV-vaccinated and naturally FIV-infected cats. The performance of three commercially available point-of-care antibody test kits was compared in a mixed population of FIV-vaccinated (n=119) and FIV-unvaccinated (n=239) cats in Australia. FIV infection status was assigned by considering the results of all antibody kits in concert with results from a commercially available PCR assay (FIV RealPCR™). Two lateral flow immunochromatography test kits (Witness FeLV/FIV; Anigen Rapid FIV/FeLV) had excellent overall sensitivity (100%; 100%) and specificity (98%; 100%) and could discern the true FIV infection status of cats, irrespective of FIV vaccination history. The lateral flow ELISA test kit (SNAP FIV/FeLV Combo) could not determine if antibodies detected were due to previous FIV vaccination, natural FIV infection, or both. The sensitivity and specificity of FIV RealPCR™ for detection of viral and proviral nucleic acid was 92% and 99%, respectively. These results will potentially change the way veterinary practitioners screen for FIV in jurisdictions where FIV vaccination is practiced, especially in shelter scenarios where the feasibility of mass screening is impacted by the cost of testing.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Síndrome de Imunodeficiência Adquirida Felina/diagnóstico
Síndrome de Imunodeficiência Adquirida Felina/imunologia
Vírus da Imunodeficiência Felina/imunologia
Proteínas Oncogênicas de Retroviridae/imunologia
Testes Sorológicos/veterinária
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Animais
Austrália
Gatos
Ensaio de Imunoadsorção Enzimática/veterinária
Síndrome de Imunodeficiência Adquirida Felina/sangue
Imunocromatografia/veterinária
Sistemas Automatizados de Assistência Junto ao Leito
Reação em Cadeia da Polimerase/veterinária
Kit de Reagentes para Diagnóstico/veterinária
Sensibilidade e Especificidade
Vacinação/veterinária
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Reagent Kits, Diagnostic); 0 (Retroviridae Proteins, Oncogenic); 0 (Viral Vaccines); 0 (feline leukemia virus vaccine)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151120
[Lr] Data última revisão:
151120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151014
[St] Status:MEDLINE


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[PMID]:26430873
[Au] Autor:Abe S; Yamamoto K; Kurata M; Abe-Suzuki S; Horii R; Akiyama F; Kitagawa M
[Ad] Endereço:Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
[Ti] Título:Targeting MCM2 function as a novel strategy for the treatment of highly malignant breast tumors.
[So] Source:Oncotarget;6(33):34892-909, 2015 Oct 27.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Highly malignant tumors express high levels of the minichromosome maintenance 2 (MCM2) protein, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound MCM2, impaired its nuclear translocation, and enhanced DNA-damage-induced apoptosis in FLV-infected hematopoietic cells when the cells expressed high levels of MCM2. Here, we show that MCM2 is highly expressed in clinical samples of invasive carcinoma of the breast, especially triple-negative breast cancer (TNBC), and in cancer stem cell (CSC) marker-positive breast cancer cells. To generate a cancer therapy model using gp70, we introduced the gp70 protein into the cytoplasm of murine breast cancer cells that express high levels of MCM2 by conjugating the protein transduction domain (PTD) of Hph-1 to gp70 (Hph-1-gp70). Hph-1-gp70 was successfully transduced into the cytoplasm of breast cancer cells. The transduced protein enhanced the DNA damage-induced apoptosis of cancer cells in vitro and in vivo. Therefore, an MCM2-targeted strategy using Hph-1-gp70 treatment to induce DNA damage might be a successful therapy for highly malignant breast cancers such as TNBC and for the eradication of CSC-like cells from breast cancer tissue.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias da Mama/metabolismo
Carcinoma Ductal de Mama/metabolismo
Componente 2 do Complexo de Manutenção de Minicromossomo/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/patologia
Feminino
Imunofluorescência
Seres Humanos
Immunoblotting
Imuno-Histoquímica
Imunoprecipitação
Marcação In Situ das Extremidades Cortadas
Masculino
Camundongos
Camundongos SCID
Meia-Idade
Complexo Repressor Polycomb 1/farmacologia
RNA Interferente Pequeno
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Recombinantes de Fusão/farmacologia
Proteínas Oncogênicas de Retroviridae/farmacologia
Transdução Genética
Transfecção
Proteínas do Envelope Viral/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (PHC1 protein, human); 0 (RNA, Small Interfering); 0 (Recombinant Fusion Proteins); 0 (Retroviridae Proteins, Oncogenic); 0 (Viral Envelope Proteins); 0 (glycoprotein gp70, Feline leukemia virus); EC 2.3.2.27 (Polycomb Repressive Complex 1); EC 3.6.4.12 (MCM2 protein, human); EC 3.6.4.12 (Minichromosome Maintenance Complex Component 2)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151003
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.5408


  9 / 1730 MEDLINE  
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[PMID]:26085154
[Au] Autor:Russell RF; McDonald JU; Ivanova M; Zhong Z; Bukreyev A; Tregoning JS
[Ad] Endereço:Mucosal Infection and Immunity Group, Section of Virology, Department of Medicine, St. Mary's Campus, Imperial College London, London, United Kingdom.
[Ti] Título:Partial Attenuation of Respiratory Syncytial Virus with a Deletion of a Small Hydrophobic Gene Is Associated with Elevated Interleukin-1ß Responses.
[So] Source:J Virol;89(17):8974-81, 2015 Sep.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuated in vivo, but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSH in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1ß (IL-1ß) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1ß was blocked in vivo, the viral load returned to wild-type levels. A significantly greater IL-1ß response to RSV ΔSH was also detected in vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1ß response in vivo, the first demonstration of neutrophilic IL-1ß production in response to viral lung infection. In this study, we describe an increased IL-1ß response to RSV ΔSH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines. IMPORTANCE: There is a pressing need for a vaccine for respiratory syncytial virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved, showing it is a pore-forming protein (viroporin). Here, we demonstrate that the IL-1ß response to RSV ΔSH is greater in spite of a lower viral load, which contributes to the attenuation in vivo. This potentially suggests a novel method by which viruses can evade the host response. As all Pneumovirinae and some Paramyxovirinae carry similar SH genes, this new understanding may also enable the development of live attenuated vaccines for both RSV and other members of the Paramyxoviridae.
[Mh] Termos MeSH primário: Interleucina-1beta/imunologia
Infecções por Vírus Respiratório Sincicial/imunologia
Vírus Sinciciais Respiratórios/genética
Vírus Sinciciais Respiratórios/imunologia
Proteínas Oncogênicas de Retroviridae/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Células Epiteliais/imunologia
Células Epiteliais/virologia
Feminino
Deleção de Genes
Técnicas de Inativação de Genes
Seres Humanos
Interleucina-1beta/biossíntese
Macrófagos/imunologia
Macrófagos/virologia
Camundongos
Camundongos Endogâmicos BALB C
Neutrófilos/imunologia
Neutrófilos/virologia
Infecções por Vírus Respiratório Sincicial/virologia
Vacinas contra Vírus Sincicial Respiratório/imunologia
Vírus Sinciciais Respiratórios/crescimento & desenvolvimento
Vacinação
Vacinas Atenuadas/imunologia
Carga Viral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (IL1B protein, mouse); 0 (Interleukin-1beta); 0 (Respiratory Syncytial Virus Vaccines); 0 (Retroviridae Proteins, Oncogenic); 0 (Vaccines, Attenuated); 0 (small hydrophobic protein, virus)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150619
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.01070-15


  10 / 1730 MEDLINE  
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[PMID]:26053927
[Au] Autor:Torres J; Surya W; Li Y; Liu DX
[Ad] Endereço:School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. jtorres@ntu.edu.sg.
[Ti] Título:Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?
[So] Source:Viruses;7(6):2858-83, 2015 Jun 04.
[Is] ISSN:1999-4915
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity.
[Mh] Termos MeSH primário: Coronavirus/fisiologia
Paramyxovirinae/fisiologia
Porinas/metabolismo
Proteínas Oncogênicas de Retroviridae/metabolismo
Proteínas do Envelope Viral/metabolismo
[Mh] Termos MeSH secundário: Animais
Antivirais/isolamento & purificação
Antivirais/farmacologia
Deleção de Genes
Seres Humanos
Ligação Proteica
Conformação Proteica
Mapeamento de Interação de Proteínas
Proteínas Oncogênicas de Retroviridae/antagonistas & inibidores
Proteínas Oncogênicas de Retroviridae/genética
Técnicas do Sistema de Duplo-Híbrido
Proteínas do Envelope Viral/antagonistas & inibidores
Proteínas do Envelope Viral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Porins); 0 (Retroviridae Proteins, Oncogenic); 0 (Viral Envelope Proteins); 0 (small hydrophobic protein, virus)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150803
[Lr] Data última revisão:
150803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150609
[St] Status:MEDLINE
[do] DOI:10.3390/v7062750



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