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[PMID]:29458688
[Au] Autor:Mitchell SL; Chang YC; Feemster K; Cárdenas AM
[Ad] Endereço:1​Clinical Microbiology Laboratory, Children's Hospital of Pittsburgh of UPMC and Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
[Ti] Título:Implementation of a rapid influenza A/B and RSV direct molecular assay improves emergency department oseltamivir use in paediatric patients.
[So] Source:J Med Microbiol;67(3):358-363, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Influenza A virus (FluA), influenza B virus (FluB) and respiratory syncytial virus (RSV) illnesses increase hospitalizations during seasonal epidemics. METHODOLOGY: To determine the utility of the Simplexa FluA/B & RSV Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this assay to emergency department (ED) patients with influenza-like illness. RESULTS: Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours. Compared to the flu season prior to implementation of the Direct Flu/RSV, clinicians were more likely to prescribe 5 days of oseltamivir therapy for Direct Flu/RSV-positive patients in comparison to those with a negative test. CONCLUSIONS: Use of Direct Flu/RSV provides results rapidly, which leads to more appropriate use of oseltamivir. The ease of use of this assay and quick TAT allows for prompt decision-making, which is essential for patient care and effective disease control during the influenza season.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Influenza Humana/diagnóstico
Influenza Humana/tratamento farmacológico
Técnicas de Diagnóstico Molecular
Oseltamivir/uso terapêutico
Infecções por Vírus Respiratório Sincicial/diagnóstico
[Mh] Termos MeSH secundário: Antivirais/administração & dosagem
Criança
Saúde da Criança
Pré-Escolar
Serviço Hospitalar de Emergência
Feminino
Seres Humanos
Vírus da Influenza A/genética
Vírus da Influenza A/isolamento & purificação
Vírus da Influenza B/genética
Vírus da Influenza B/isolamento & purificação
Influenza Humana/virologia
Masculino
Nasofaringe/virologia
Oseltamivir/administração & dosagem
Kit de Reagentes para Diagnóstico
Reação em Cadeia da Polimerase em Tempo Real
Infecções por Vírus Respiratório Sincicial/virologia
Vírus Sinciciais Respiratórios/genética
Vírus Sinciciais Respiratórios/isolamento & purificação
Sensibilidade e Especificidade
Resultado do Tratamento
Viroses/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Reagent Kits, Diagnostic); 20O93L6F9H (Oseltamivir)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000676


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[PMID]:28469033
[Au] Autor:Zhu Q; McLellan JS; Kallewaard NL; Ulbrandt ND; Palaszynski S; Zhang J; Moldt B; Khan A; Svabek C; McAuliffe JM; Wrapp D; Patel NK; Cook KE; Richter BWM; Ryan PC; Yuan AQ; Suzich JA
[Ad] Endereço:Department of Infectious Disease, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA. suzichj@medimmune.com zhuq@medimmune.com.
[Ti] Título:A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants.
[So] Source:Sci Transl Med;9(388), 2017 May 03.
[Is] ISSN:1946-6242
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897*, a highly potent human antibody, was optimized from antibody D25, which targets the prefusion conformation of the RSV fusion (F) protein. Crystallographic analysis of Fab in complex with RSV F from subtypes A and B reveals that MEDI8897* binds a highly conserved epitope. MEDI8897* neutralizes a diverse panel of RSV A and B strains with >50-fold higher activity than palivizumab. At similar serum concentrations, prophylactic administration of MEDI8897* was ninefold more potent than palivizumab at reducing pulmonary viral loads by >3 logs in cotton rats infected with either RSV A or B subtypes. MEDI8897 was generated by the introduction of triple amino acid substitutions (YTE) into the Fc domain of MEDI8897*, which led to more than threefold increased half-life in cynomolgus monkeys compared to non-YTE antibody. Considering the pharmacokinetics of palivizumab in infants, which necessitates five monthly doses for protection during an RSV season, the high potency and extended half-life of MEDI8897 support its development as a cost-effective option to protect all infants from RSV disease with once-per-RSV-season dosing in the clinic.
[Mh] Termos MeSH primário: Palivizumab/uso terapêutico
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/uso terapêutico
Vírus Sinciciais Respiratórios/patogenicidade
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/uso terapêutico
Anticorpos Monoclonais Humanizados/uso terapêutico
Antivirais/farmacocinética
Antivirais/uso terapêutico
Feminino
Seres Humanos
Lactente
Recém-Nascido
Masculino
Palivizumab/farmacocinética
Infecções por Vírus Respiratório Sincicial/tratamento farmacológico
Vírus Sinciciais Respiratórios/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Monoclonal, Humanized); 0 (Antiviral Agents); 0 (Respiratory Syncytial Virus Vaccines); DQ448MW7KS (Palivizumab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


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[PMID]:29258592
[Au] Autor:Yoon BW; Lee SH
[Ad] Endereço:Department of Internal Medicine, Hanil General Hospital, Seoul, Republic of Korea.
[Ti] Título:Possible therapeutic effect of orally administered ribavirin for respiratory syncytial virus-induced acute respiratory distress syndrome in an immunocompetent patient: a case report.
[So] Source:J Med Case Rep;11(1):353, 2017 Dec 20.
[Is] ISSN:1752-1947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Human respiratory syncytial virus usually causes self-limiting upper respiratory infection and occasionally causes pneumonia in immunocompromised hosts. Respiratory syncytial virus-induced severe pneumonia or acute respiratory distress syndrome in immunocompetent adults has been rarely described. Unfortunately, optimal treatment has not been established for this potentially fatal condition. We report a case of respiratory syncytial virus-induced acute respiratory distress syndrome occurring in a previously healthy man successfully treated with orally administered ribavirin. CASE PRESENTATION: An 81-year-old previously healthy Korean man presented with cough, dyspnea, and febrile sensation. He had hypoxemia with diffuse ground glass opacity evident on chest radiography, which progressed and required mechanical ventilation. All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus. Under the diagnosis of respiratory syncytial virus-induced acute respiratory distress syndrome, orally administered ribavirin was administered and he recuperated completely without complications. CONCLUSION: This case demonstrates the potential usefulness of orally administered ribavirin as a therapeutic option for severe respiratory syncytial virus infection, at least in an immunocompetent host.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Imunocompetência
Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico
Infecções por Vírus Respiratório Sincicial/tratamento farmacológico
Ribavirina/uso terapêutico
[Mh] Termos MeSH secundário: Administração Oral
Idoso de 80 Anos ou mais
Seres Humanos
Masculino
Reação em Cadeia da Polimerase em Tempo Real
Síndrome do Desconforto Respiratório do Adulto/etiologia
Síndrome do Desconforto Respiratório do Adulto/virologia
Infecções por Vírus Respiratório Sincicial/complicações
Infecções por Vírus Respiratório Sincicial/diagnóstico
Vírus Sinciciais Respiratórios/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 49717AWG6K (Ribavirin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1186/s13256-017-1514-x


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[PMID]:29182682
[Au] Autor:Cayatte C; Snell Bennett A; Rajani GM; Hostetler L; Maynard SK; Lazzaro M; McTamney P; Ren K; O'Day T; McCarthy MP; Schneider-Ohrum K
[Ad] Endereço:Department of Infectious Diseases/Vaccines, MedImmune, Gaithersburg, Maryland, United States of America.
[Ti] Título:Inferior immunogenicity and efficacy of respiratory syncytial virus fusion protein-based subunit vaccine candidates in aged versus young mice.
[So] Source:PLoS One;12(11):e0188708, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Respiratory syncytial virus (RSV) is recognized as an important cause of lower and upper respiratory tract infections in older adults, and a successful vaccine would substantially lower morbidity and mortality in this age group. Recently, two vaccine candidates based on soluble purified glycoprotein F (RSV F), either alone or adjuvanted with glucopyranosyl lipid A formulated in a stable emulsion (GLA-SE), failed to reach their primary endpoints in clinical efficacy studies, despite demonstrating the desired immunogenicity profile and efficacy in young rodent models. Here, one of the RSV F vaccine candidates (post-fusion conformation, RSV post-F), and a stabilized pre-fusion form of RSV F (RSV pre-F, DS-Cav1) were evaluated in aged BALB/c mice. Humoral and cellular immunogenicity elicited after immunization of naïve, aged mice was generally lower compared to young animals. In aged mice, RSV post-F vaccination without adjuvant poorly protected the respiratory tract from virus replication, and addition of GLA-SE only improved protection in the lungs, but not in nasal turbinates. RSV pre-F induced higher neutralizing antibody titers compared to RSV post-F (as previously reported) but interestingly, RSV F-specific CD8 T cell responses were lower compared to RSV post-F responses regardless of age. The vaccines were also tested in RSV seropositive aged mice, in which both antigen forms similarly boosted neutralizing antibody titers, although GLA-SE addition boosted neutralizing activity only in RSV pre-F immunized animals. Cell-mediated immune responses in the aged mice were only slightly boosted and well below levels induced in seronegative young mice. Taken together, the findings suggest that the vaccine candidates were not able to induce a strong anti-RSV immune response in recipient mice with an aged immune system, in agreement with recent human clinical trial results. Therefore, the aged mouse model could be a useful tool to evaluate improved vaccine candidates, targeted to prevent RSV disease in older adults.
[Mh] Termos MeSH primário: Fatores Etários
Proteínas Recombinantes de Fusão/imunologia
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/imunologia
Vírus Sinciciais Respiratórios/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/biossíntese
Seres Humanos
Imunidade Celular
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Vírus Respiratório Sincicial/imunologia
Vírus Sinciciais Respiratórios/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Recombinant Fusion Proteins); 0 (Respiratory Syncytial Virus Vaccines)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188708


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[PMID]:29049206
[Au] Autor:Saraya T; Kimura H; Kurai D; Ishii H; Takizawa H
[Ad] Endereço:aKyorin University School of Medicine, Department of Respiratory Medicine, Mitaka City bInfectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan.
[Ti] Título:The molecular epidemiology of respiratory viruses associated with asthma attacks: A single-center observational study in Japan.
[So] Source:Medicine (Baltimore);96(42):e8204, 2017 Oct.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Few reports have described the significance of viral respiratory infections (VRIs) in exacerbation of asthma in adult patients. The aim of this study was to elucidate the profiles of VRIs in adult patients with asthma along with their molecular epidemiology.A cross-sectional observational study was conducted at Kyorin University Hospital from August 2012 to May 2015. To identify respiratory pathogens in inpatients and outpatients suffering from asthma attacks, RT-PCR/sequencing/phylogenetic analysis methods were applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed.A total of 106 asthma attack patients enrolled in this study in both inpatient (n = 49) and outpatient (n = 57) settings. The total 106 respiratory samples were obtained from nasopharyngeal swab (n = 68) or sputum (n = 38). Among these, patients with virus alone (n = 39), virus and bacterial (n = 5), and bacterial alone (n = 5) were identified. The ratio of virus-positive patients in inpatient or outpatient to the total cases were 31.1% (n = 33) and 10.4% (n = 11), respectively. The frequency of virus-positive patients was significantly higher in inpatients (75.3%, n = 33) than in outpatients (19.3%, n = 11). Major VRIs included human rhinovirus (HRV) (n = 24), human metapneumovirus (hMPV) (n = 9), influenza virus (Inf-V) (n = 8), and respiratory syncytial virus (RSV) (n = 3) infections with seasonal variations. HRV-A and HRV-C were the most commonly detected viruses, with wide genetic divergence on phylogenetic analysis.Asthmatic exacerbations in adults are highly associated with VRIs such as HRV-A or HRV-C, hMPV, RSV, and Inf-V infections with seasonal variations and genetic divergence, but similar frequencies of VRIs occurred in asthma attack patients throughout the seasons.
[Mh] Termos MeSH primário: Asma/virologia
Vírus de RNA/genética
Infecções Respiratórias/epidemiologia
Viroses/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Infecções Bacterianas/complicações
Infecções Bacterianas/epidemiologia
Estudos Transversais
Feminino
Genótipo
Seres Humanos
Pacientes Internados/estatística & dados numéricos
Japão/epidemiologia
Masculino
Metapneumovirus/genética
Metapneumovirus/isolamento & purificação
Meia-Idade
Nasofaringe/virologia
Orthomyxoviridae/genética
Orthomyxoviridae/isolamento & purificação
Pacientes Ambulatoriais/estatística & dados numéricos
Filogenia
Vírus de RNA/isolamento & purificação
Vírus Sinciciais Respiratórios/genética
Vírus Sinciciais Respiratórios/isolamento & purificação
Infecções Respiratórias/virologia
Rhinovirus/genética
Rhinovirus/isolamento & purificação
Estações do Ano
Escarro/virologia
Viroses/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008204


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[PMID]:28987219
[Au] Autor:Jartti T; Gern JE
[Ad] Endereço:Department of Paediatrics, Turku University Hospital and University of Turku, Turku, Finland. Electronic address: tuomas.jartti@utu.fi.
[Ti] Título:Role of viral infections in the development and exacerbation of asthma in children.
[So] Source:J Allergy Clin Immunol;140(4):895-906, 2017 Oct.
[Is] ISSN:1097-6825
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.
[Mh] Termos MeSH primário: Asma/imunologia
Microbiota/imunologia
Vírus Sinciciais Respiratórios/imunologia
Rhinovirus/imunologia
Viroses/imunologia
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/uso terapêutico
Asma/tratamento farmacológico
Bronquiolite
Criança
Progressão da Doença
Seres Humanos
Palivizumab/uso terapêutico
Sons Respiratórios
Vírus Sinciciais Respiratórios/patogenicidade
Rhinovirus/patogenicidade
Risco
Virulência
Viroses/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); DQ448MW7KS (Palivizumab)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


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[PMID]:28963880
[Au] Autor:Rajan D; Chinnadurai R; Keefe EO; Boyoglu-Barnum S; Todd SO; Hartert TV; Galipeau J; Anderson LJ
[Ad] Endereço:Department of Pediatrics, Emory Children's Center, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia.
[Ti] Título:Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells.
[So] Source:Virology;512:144-150, 2017 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RSV is a major cause of severe lower respiratory infection in infants and young children. With no vaccine yet available, it is important to clarify mechanisms of disease pathogenesis. Since indoleamine-2,3-dioxygenase (IDO) is an immunomodulatory enzyme and is upregulated with RSV infection, we studied it in vivo during infection of BALB/c mice and in vitro in A549 cells. RSV infection upregulated IDO transcripts in vivo and in vitro. IDO siRNA decreased IDO transcripts ~2 fold compared to control siRNA after RSV infection but this decrease did not affect RSV replication. In the presence of IFN-γ, siRNA-induced a decrease in IDO expression that was associated with an increase in virus replication and increased levels of IL-6, IL-8, CXCL10 and CCL4. Thus, our results show IDO is upregulated with RSV infection and this upregulation likely participates with IFN-γ in inhibition of virus replication and suppression of some host cell responses to infection.
[Mh] Termos MeSH primário: Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Vírus Sinciciais Respiratórios/imunologia
[Mh] Termos MeSH secundário: Células A549
Animais
Citocinas/metabolismo
Feminino
Regulação da Expressão Gênica/fisiologia
Seres Humanos
Indolamina-Pirrol 2,3,-Dioxigenase/genética
Camundongos
Camundongos Endogâmicos BALB C
Interferência de RNA
Regulação para Cima
Replicação Viral/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171001
[St] Status:MEDLINE


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[PMID]:28901900
[Au] Autor:Xiang Z; Liang Z; Yanfeng H; Leitao K
[Ad] Endereço:1​Cancer Hospital of China Medical University, 44 Xiaoheyan Road, Dadong Region, Shengyang 110042, Liaoning, PR China.
[Ti] Título:Persistence of RSV promotes proliferation and epithelial-mesenchymal transition of bronchial epithelial cells through Nodal signaling.
[So] Source:J Med Microbiol;66(10):1499-1505, 2017 Oct.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Nodal may play an important role in the development of cancers. The present study was designed to determine the effects of Nodal induced by respiratory syncytial virus (RSV) infection on the occurrence and development of lung cancer and the underlying mechanisms. METHODOLOGY: After verification of RSV infection by observation of cytopathic effect and indirect immunofluorescence, real-time PCR, Western blot and methylation assays were used to verify the influence of RSV on Nodal expression. Then, a Nodal overexpressed vector was constructed and the effects of Nodal on the proliferation and apoptosis of bronchial epithelial cells (BECs) and epithelial-mesenchymal transition (EMT) were assayed by flow cytometry and Western blot, respectively. Moreover, Lefty and pSmad2/3 were assayed by Western blot and Cyclin D1, CDK4, c-myc and Bcl-2 induced by Nodal overepression or RSV infection were also assayed by real-time PCR. RESULTS: The results showed that Nodal over expression and demethylation of the promoter were observed in BECs after RSV infection. Activation of Nodal promoted proliferation, colony formation and EMT and inhibited apoptosis of BECs. Nodal also promoted malignant change by promoting expression of cyclin D1 and related-dependent kinase and inhibiting apoptosis. Besides, RSV infection inhibited Lefty expression and promoted the activation of pSmad2/3. RSV also promoted Cyclin D1, CDK4, c-myc and Bcl-2 expression through the activation of pSmad2/3. CONCLUSIONS: Our data showed that persistence of RSV promoted the proliferation, epithelial-mesenchymal transition and expression of oncogenes through Nodal signaling, which may be associated with the occurrence and development of lung cancers.
[Mh] Termos MeSH primário: Células Epiteliais/virologia
Transição Epitelial-Mesenquimal/fisiologia
Proteína Nodal/metabolismo
Mucosa Respiratória/citologia
Infecções por Vírus Respiratório Sincicial/complicações
[Mh] Termos MeSH secundário: Ciclina D1/genética
Ciclina D1/metabolismo
Quinase 4 Dependente de Ciclina/genética
Quinase 4 Dependente de Ciclina/metabolismo
Efeito Citopatogênico Viral
Células Epiteliais/fisiologia
Regulação da Expressão Gênica/fisiologia
Genes myc/genética
Genes myc/fisiologia
Células HeLa
Seres Humanos
Proteína Nodal/genética
Proteínas Proto-Oncogênicas c-bcl-2/genética
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Infecções por Vírus Respiratório Sincicial/virologia
Vírus Sinciciais Respiratórios
Proteínas Smad/genética
Proteínas Smad/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NODAL protein, human); 0 (Nodal Protein); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Smad Proteins); 136601-57-5 (Cyclin D1); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000581


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[PMID]:28846899
[Au] Autor:Hwang HS; Lee YT; Kim KH; Ko EJ; Lee Y; Kwon YM; Kang SM
[Ad] Endereço:Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
[Ti] Título:Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.
[So] Source:Virology;511:142-151, 2017 Nov.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia.
[Mh] Termos MeSH primário: Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/efeitos adversos
Vacinas contra Vírus Sincicial Respiratório/imunologia
Vírus Sinciciais Respiratórios/imunologia
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD8-Positivos/imunologia
Citocinas/secreção
Camundongos
Células Th1/imunologia
Vacinas de Produtos Inativados/efeitos adversos
Vacinas de Produtos Inativados/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Respiratory Syncytial Virus Vaccines); 0 (Vaccines, Inactivated); 0 (Vaccines, Virus-Like Particle)
[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:170829
[St] Status:MEDLINE


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[PMID]:28835504
[Au] Autor:Liu X; Liang B; Ngwuta J; Liu X; Surman S; Lingemann M; Kwong PD; Graham BS; Collins PL; Munir S
[Ad] Endereço:RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
[Ti] Título:Attenuated Human Parainfluenza Virus Type 1 Expressing the Respiratory Syncytial Virus (RSV) Fusion (F) Glycoprotein from an Added Gene: Effects of Prefusion Stabilization and Packaging of RSV F.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human respiratory syncytial virus (RSV) is the most prevalent worldwide cause of severe respiratory tract infection in infants and young children. Human parainfluenza virus type 1 (HPIV1) also causes severe pediatric respiratory illness, especially croup. Both viruses lack vaccines. Here, we describe the preclinical development of a bivalent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, attenuated by a stabilized mutation, that expresses RSV F protein modified for increased stability in the prefusion (pre-F) conformation by previously described disulfide bond (DS) and hydrophobic cavity-filling (Cav1) mutations. RSV F was expressed from the first or second gene position as the full-length protein or as a chimeric protein with its transmembrane and cytoplasmic tail (TMCT) domains substituted with those of HPIV1 F in an effort to direct packaging in the vector particles. All constructs were recovered by reverse genetics. The TMCT versions of RSV F were packaged in the rHPIV1 particles much more efficiently than their full-length counterparts. In hamsters, the presence of the RSV F gene, and in particular the TMCT versions, was attenuating and resulted in reduced immunogenicity. However, the vector expressing full-length RSV F from the pre-N position was immunogenic for RSV and HPIV1. It conferred complement-independent high-quality RSV-neutralizing antibodies at titers similar to those of wild-type RSV and provided protection against RSV challenge. The vectors exhibited stable RSV F expression and In conclusion, an attenuated rHPIV1 vector expressing a pre-F-stabilized form of RSV F demonstrated promising immunogenicity and should be further developed as an intranasal pediatric vaccine. RSV and HPIV1 are major viral causes of acute pediatric respiratory illness for which no vaccines or suitable antiviral drugs are available. The RSV F glycoprotein is the major RSV neutralization antigen. We used a rHPIV1 vector, bearing a stabilized attenuating mutation, to express the RSV F glycoprotein bearing amino acid substitutions that increase its stability in the pre-F form, the most immunogenic form that elicits highly functional virus-neutralizing antibodies. RSV F was expressed from the pre-N or N-P gene position of the rHPIV1 vector as a full-length protein or as a chimeric form with its TMCT domain derived from HPIV1 F. TMCT modification greatly increased packaging of RSV F into the vector particles but also increased vector attenuation , resulting in reduced immunogenicity. In contrast, full-length RSV F expressed from the pre-N position was immunogenic, eliciting complement-independent RSV-neutralizing antibodies and providing protection against RSV challenge.
[Mh] Termos MeSH primário: Expressão Gênica
Vetores Genéticos
Vírus da Parainfluenza 1 Humana/fisiologia
Infecções por Vírus Respiratório Sincicial
Vacinas contra Vírus Sincicial Respiratório
Vírus Sinciciais Respiratórios
Proteínas Virais de Fusão
Montagem de Vírus
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/imunologia
Anticorpos Antivirais/imunologia
Cercopithecus aethiops
Cobaias
Seres Humanos
Mesocricetus
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Infecções por Vírus Respiratório Sincicial/genética
Infecções por Vírus Respiratório Sincicial/imunologia
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/genética
Vacinas contra Vírus Sincicial Respiratório/imunologia
Vírus Sinciciais Respiratórios/genética
Vírus Sinciciais Respiratórios/imunologia
Células Vero
Proteínas Virais de Fusão/genética
Proteínas Virais de Fusão/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Recombinant Proteins); 0 (Respiratory Syncytial Virus Vaccines); 0 (Viral Fusion Proteins)
[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:170825
[St] Status:MEDLINE



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