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1.
Internist (Berl) ; 60(11): 1146-1150, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31486858

RESUMO

Respiratory syncytial virus (RSV) is worldwide a very important virus leading to infection of the respiratory system. In particular preterm babies, infants and elderly adults are prone to developing severe diseases such as bronchiolitis or pneumonia, which require intensive care and cause increased mortality. Although RSV is rapidly detected, preventive and therapeutic measures are limited. New antivirals are already in clinical trials.


Assuntos
Antivirais/administração & dosagem , Bronquiolite/diagnóstico , Bronquiolite/prevenção & controle , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/isolamento & purificação , Adulto , Idoso , Antivirais/uso terapêutico , Bronquiolite/tratamento farmacológico , Bronquiolite/virologia , Bronquiolite Viral/diagnóstico , Bronquiolite Viral/virologia , Humanos , Lactente , Recém-Nascido , Pneumonia/diagnóstico , Pneumonia/virologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Fatores de Risco
3.
PLoS One ; 14(3): e0213501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845274

RESUMO

Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection-comparatively to HRV infection-was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.


Assuntos
Bronquiolite Viral/metabolismo , Regulação Viral da Expressão Gênica , Hospitalização , Neutrófilos/metabolismo , Infecções por Picornaviridae/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Vírus Sinciciais Respiratórios/metabolismo , Rhinovirus/metabolismo , Transcrição Genética , Bronquiolite Viral/terapia , Bronquiolite Viral/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neutrófilos/virologia , Infecções por Picornaviridae/terapia , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/terapia
4.
Eur J Pediatr ; 178(2): 131-138, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30610420

RESUMO

Respiratory syncytial virus (RSV) infection is one of the main causes of infant hospitalization and mortality. The single-stranded RNA virus codes for 11 proteins of which the F protein, a surface epitope responsible for RSV fusion, is the most targeted for developing antiviral medicines and vaccines. The peak of symptoms occurs around day 4 to 6 of illness and the airway obstruction is merely caused by the host immune inflammatory response. Risk factors for severe bronchiolitis are prematurity, comorbidity, and/or being immunocompromised. At present, there are no curative therapies available for RSV infections and treatment is supportive only. Development of new antiviral medicines is however promising. The aim of this review is to give a summary of the most important new antiviral therapies in clinical development for RSV infection and to explain their mode of action. We therefore performed a literature search on this topic.Conclusion: There are currently at least eight antivirals being investigated in clinical trials. They all use different approaches to either focus on preventing viral fusion with host cells or inhibiting virus replication. Some target RSV surface epitopes like the F protein to halt fusion, others aim for RNA chain termination, while small interfering RNAs downregulate viral protein production. What is known: • RSV bronchiolitis is a very important pediatric disease as it is one of the main causes of infant hospitalization and mortality. By the age of 2 years, 95% of all the infants worldwide will have been infected. • The only recommended therapy is supportive since there are no existing curative therapies yet. What this study adds: • This review gives an overview of the current progress in the research field of RSV antivirals with background information on their mode of action.


Assuntos
Antivirais/uso terapêutico , Bronquiolite Viral/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Bronquiolite Viral/virologia , Criança , Pré-Escolar , Humanos , Lactente
5.
Enferm Infecc Microbiol Clin ; 37(4): 251-255, 2019 04.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30100097

RESUMO

INTRODUCTION: Passive transplacental immunity against respiratory syncytial virus (RSV) appears to mediate in the protection of the infant for the first 6 months of life. Lower environmental exposure in pregnant women to RSV epidemic may influence the susceptibility of these infants to infection by lowering the levels of antibodies that are transferred to the fetus. OBJECTIVES: To contrast the risk of severe disease progression in infants with acute bronchiolitis by RSV, according to the mother's level of exposure to epidemic. METHOD: Retrospective cohort study of previously healthy infants with RSV-acute bronchiolitis during 5 epidemics was made. We compared the severity of the infection in those born during the period of risk (when is less likely the mother's exposure to epidemic and the transfer of antibodies to the fetus: October 15th-December 15th in our latitude) with the rest of acute bronchiolitis. Bivariate analysis was performed regarding birth in period of risk and the rest of variables, using the Chi-square test. Multivariate logistic regression analysis was performed to study possible classical confounding factors. RESULTS: 695 infants were included in the study. 356 infants were born during the period of risk. Of the 56 patients requiring admission to PICU, 40 of them (71.4%) were born in this period (p=0.002). In the multivariate analysis, the birth in the period of risk showed a 6.5 OR (95% CI: 2.13-19.7) independently of the rest of variables. CONCLUSIONS: The worst clinical disease progression of the acute bronchiolitis by the RSV in less than 6 months age is related to lower exposure of the pregnant woman to the RSV epidemic.


Assuntos
Bronquiolite Viral/imunologia , Bronquiolite Viral/virologia , Imunidade Materno-Adquirida/imunologia , Exposição Materna , Gravidez/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Doença Aguda , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Nat Commun ; 9(1): 2789, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018336

RESUMO

Interferon (IFN)-stimulated genes (ISGs) play crucial roles in the antiviral immune response; however, IFNs also induce negative regulators that attenuate the antiviral response. Here, we show that both viral and bacterial invasion downregulate Nuclear Dbf2-related kinase 1 (NDR1) expression via the type I IFN signaling pathway. NDR1 promotes the virus-induced production of type I IFN, proinflammatory cytokines and ISGs in a kinase-independent manner. NDR1 deficiency also renders mice more susceptible to viral and bacterial infections. Mechanistically, NDR1 enhances STAT1 translation by directly binding to the intergenic region of miR146a, thereby inhibiting miR146a expression and liberating STAT1 from miR146a-mediated translational inhibition. Furthermore, STAT1 binds to the miR146a promoter, thus decreasing its expression. Together, our results suggest that NDR1 promotion of STAT1 translation is an important event for IFN-dependent antiviral immune response, and suggest that NDR1 has an important role in controlling viral infections.


Assuntos
Bronquiolite Viral/genética , Retroalimentação Fisiológica , Herpesvirus Humano 1/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Fator de Transcrição STAT1/genética , Vírus da Estomatite Vesicular Indiana/genética , Animais , Bronquiolite Viral/imunologia , Bronquiolite Viral/virologia , Estudos de Casos e Controles , Criança , Regulação da Expressão Gênica , Células HEK293 , Herpesvirus Humano 1/imunologia , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Interferon-alfa/genética , Interferon-alfa/imunologia , Interferon beta/genética , Interferon beta/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/imunologia , Biossíntese de Proteínas , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/imunologia , Células RAW 264.7 , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Fator de Transcrição STAT1/imunologia , Transdução de Sinais , Vírus da Estomatite Vesicular Indiana/imunologia
8.
Am J Respir Crit Care Med ; 198(8): 1074-1084, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-29688024

RESUMO

RATIONALE: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an excessive immune response, or both. OBJECTIVES: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. METHODS: Infants with viral bronchiolitis necessitating admission (n = 55) were recruited from a pediatric center during 2016 and 2017. Of these, 30 were RSV infected (18 "moderate" and 12 mechanically ventilated "severe"). Nasal fluids were sampled frequently over time using nasosorption devices and nasopharyngeal aspiration. Hierarchical clustering of time-weighted averages was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. MEASUREMENTS AND MAIN RESULTS: Unexpectedly, cases with severe RSV bronchiolitis had lower nasal viral loads and reduced IFN-γ and C-C chemokine ligand 5/RANTES (regulated upon activation, normal T cell expressed and secreted) levels than those with moderate disease, especially when allowance was made for disease duration (all P < 0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of nasopharyngeal aspiration samples (n = 43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. CONCLUSIONS: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C-X-C motif chemokine ligand 10)/IP-10, and type-I IFN levels than moderately ill children, but enhanced MUC5AC (mucin-5AC) and IL17A gene expression in nasal cells.


Assuntos
Bronquiolite Viral/virologia , Interferons/metabolismo , Mucosa Nasal/virologia , Insuficiência Respiratória/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Bronquiolite Viral/imunologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mucosa Nasal/imunologia , Insuficiência Respiratória/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Transcriptoma , Carga Viral
9.
J Clin Virol ; 102: 101-109, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29549834

RESUMO

BACKGROUND: As the expression of type III IFN receptor is restricted to the mucosal surfaces, its evaluation could be crucial to characterize the role of IFNλs during bronchiolitis. OBJECTIVES: This study was designed to investigate airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus (RSV) or human rhinovirus (HRV) bronchiolitis. STUDY DESIGN: Seventy-one 1-6 month old infants hospitalized with their first episode of acute RSV or HRV bronchiolitis were selected for this study. Expression of IFNLR1, IL10RB and IFN-stimulated genes (ISGs) MxA and ISG56 in cells of nasopharyngeal washings taken within the first 48 h of admission were determined by a real-time hydrolysis probe RT-PCR assay. The ability of types I and III IFNs to induce the expression of both IFNLR1 and IL10RB in vitro was also evaluated. RESULTS: Airway IFNLR1 transcript levels were significantly higher in HRV bronchiolitis infants compared to those with RSV bronchiolitis. No differences were recorded for IL10RB-mRNA between RSV or HRV infection. IFNLR1 mRNA levels increased significantly in infants infected with the C species of HRV and in those with a higher clinical score index and with an eosinophil count >3%. There were no correlations in vivo between type III IFN receptors and those of ISGs and neither IFNLR1 nor IL10RB were induced in vitro by IFNs. CONCLUSIONS: These results suggest that IFNLR1 are increased in HRV-infected infants with more severe bronchiolitis and blood eosinophilia and in those infected with the HRVC species.


Assuntos
Bronquiolite Viral/imunologia , Bronquiolite Viral/patologia , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/patologia , Receptores de Citocinas/genética , Rhinovirus/isolamento & purificação , Bronquiolite Viral/virologia , Eosinofilia/virologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/imunologia , Nasofaringe/patologia , RNA Mensageiro/metabolismo , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Rhinovirus/classificação , Rhinovirus/genética , Índice de Gravidade de Doença
10.
Am J Epidemiol ; 187(7): 1490-1500, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29351636

RESUMO

We sought to determine the real-world effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis in a population-based cohort to inform policy. The study population included infants born during 1996-2008 and enrolled in the Kaiser Permanente Northern California integrated health-care delivery system. During the RSV season (November-March), the date of RSV immunoprophylaxis administration and the following 30 days were defined as RSV immunoprophylaxis protected period(s), and all other days were defined as unprotected period(s). Numbers of bronchiolitis hospitalizations were determined using International Classification of Diseases, Ninth Revision, codes during RSV season. We used a proportional hazards model to estimate risk of bronchiolitis hospitalization when comparing infants' protected period(s) with unprotected period(s). Infants who had ever received RSV immunoprophylaxis had a 32% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.68, 95% confidence interval: 0.46, 1.00) when protected periods were compared with unprotected periods. Infants with chronic lung disease (CLD) had a 52% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.48, 95% confidence interval: 0.25, 0.94) when protected periods were compared with unprotected periods. Under the new 2014 American Academy of Pediatrics (AAP) guidelines, 48% of infants eligible for RSV immunoprophylaxis on the basis of AAP guidelines in place at birth would no longer be eligible, but nearly all infants with CLD would remain eligible. RSV immunoprophylaxis is effective in decreasing hospitalization. This association is greatest for infants with CLD, a group still recommended for receipt of RSV immunoprophylaxis under the new AAP guidelines.


Assuntos
Bronquiolite Viral/prevenção & controle , Hospitalização/estatística & dados numéricos , Imunização/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/imunologia , Antivirais/uso terapêutico , Bronquiolite Viral/epidemiologia , Bronquiolite Viral/virologia , California/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Fatores de Risco , Estações do Ano , Resultado do Tratamento
11.
J Investig Med ; 66(1): 46-51, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28947640

RESUMO

Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification.


Assuntos
Bronquiolite Viral/classificação , Bronquiolite Viral/virologia , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Masculino , Recidiva , Sons Respiratórios
12.
Gene ; 645: 7-17, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29253610

RESUMO

BACKGROUND: Acute viral bronchiolitis is the leading cause of hospitalization among infants during the first year of life. Most infants hospitalized for bronchiolitis do not present risk factors and are otherwise healthy. Our objective was to determine the genetic features associated with the risk and a severe course of bronchiolitis. METHODS: We prospectively evaluated 181 infants with severe bronchiolitis admitted at three hospitals over a 2-year period, who required oxygen therapy. The control group consisted of 536 healthy adults. Patients were evaluated for the presence of comorbidities (premature birth, chronic respiratory disease, and congenital heart disease), underwent nasopharyngeal aspirate testing for virus detection by multiplex-PCR, and SNPs identification in immune response genes. Patient outcomes were assessed. RESULTS: We observed association between SNP rs2107538*CCL5 and bronchiolitis caused by respiratory syncytial virus(RSV) and RSV-subtype-A, and between rs1060826*NOS2 and bronchiolitis caused by rhinovirus. SNPs rs4986790*TLR4, rs1898830*TLR2, and rs2228570*VDR were associated with progression to death. SNP rs7656411*TLR2 was associated with length of oxygen use; SNPs rs352162*TLR9, rs187084*TLR9, and rs2280788*CCL5 were associated with requirement for intensive care unit admission; while SNPs rs1927911*TLR4, rs352162*TLR9, and rs2107538*CCL5 were associated with the need for mechanical ventilation. CONCLUSIONS: Our findings provide some evidence that SNPs in CCL5 and NOS2 are associated with presence of bronchiolitis and SNPs in TLR4, TLR2, TLR9, VDR and CCL5 are associated with severity of bronchiolitis.


Assuntos
Bronquiolite Viral/genética , Quimiocina CCL5/genética , Óxido Nítrico Sintase Tipo II/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Receptores Toll-Like/genética , Bronquiolite Viral/virologia , Progressão da Doença , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/virologia , Estudos Retrospectivos , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genética
13.
J Pediatr (Rio J) ; 94(1): 56-61, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28506664

RESUMO

OBJECTIVE: The objective of this study is to evaluate the hypothesis that use of heliox would result in improvement of gas exchange when used with high flow nasal cannula in infants with RSV acute bronchiolitis. METHODS: All patients that met the inclusion criteria were randomized to either heliox (70:30) or air-oxygen mixture 30% via high flow nasal cannula at 8L/min for a continuous 24h. Measurements were taken at baseline, after 2h, and at the end of the 24h. RESULTS: This prospective study included 48 patients. After 2h of treatment with heliox, the oxygen saturation and PaO2 significantly improved when compared with the air-oxygen group, 98.3% vs. 92.9%, 62.0mmHg vs. 43.6mmHg (p=0.04 and 0.01), respectively. Furthermore, PaO2/FiO2 ratio was significantly higher in the heliox group when compared with the air-oxygen group, 206.7 vs. 145.3. Nevertheless, CO2 showed better elimination when heliox was used, without significance. MWCA score dropped significantly in the heliox group, 2.2 points vs. 4.0 points in air-oxygen (p=0.04), 2h after starting the therapy. CONCLUSION: Transient improvement of oxygenation in infants with RSV acute bronchiolitis during the initial phase of the therapy is associated with heliox when provided with HFNC, may provide a precious time for other therapeutic agents to work or for the disease to resolve naturally, avoiding other aggressive interventions.


Assuntos
Bronquiolite Viral/terapia , Cânula , Hélio/administração & dosagem , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Infecções por Vírus Respiratório Sincicial/terapia , Doença Aguda , Bronquiolite Viral/virologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Resultado do Tratamento
14.
J Microbiol Immunol Infect ; 51(6): 749-755, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28757139

RESUMO

BACKGROUND: Human parainfluenza viruses (HPIV) 1-4 had been analyzed as being one of the most frequent causes of hospitalizations for young children with respiratory tract illnesses. METHODS: This retrospective study was performed from children virologically confirmed as HPIV infection through throat swab or nasopharyngeal aspirates at a tertiary care university hospital, between January 2012 and December 2014. HPIV4 was not checked and analyzed, due to not include in the commercial kit. The demographic, epidemiological, clinical presentations, diagnosis, treatment, outcomes, and laboratory data were analyzed. RESULTS: Totally 398 cases were enrolled, including 39 (9.8%) of HPIV1, 67 (16.8%) of HPIV2, and 292 (73.4%) of HPIV3. The mean age of HPIV-infected children was 2.9 year-old, and 50.5% were among one to three year-old. A total of 56.8% HPIV3-infected children were among one to three years old, however, no HPIV2-infected children was younger than one year-old. The HPIV1-infected patients were more common to develop wheezing and diagnose as acute bronchiolitis. HPIV2-infected children were more likely to have hoarseness (23.9%), and were associated with croup (25.4%). HPIV3 was isolated from two fatal cases, with neurological underlying diseases. CONCLUSION: The impact caused by HPIVs infections is significant in hospitalized children. In the current study, our results contribute to the epidemiologic, clinical and laboratory information of HPIV infection in children in the important areas of respiratory tract infection that could support the development of optimization management.


Assuntos
Vírus da Parainfluenza 1 Humana/isolamento & purificação , Vírus da Parainfluenza 2 Humana/isolamento & purificação , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/epidemiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Bronquiolite Viral/diagnóstico , Bronquiolite Viral/virologia , Criança , Pré-Escolar , Crupe/diagnóstico , Crupe/virologia , Feminino , Hospitalização , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Infecções por Paramyxoviridae/patologia , Infecções por Paramyxoviridae/virologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Taiwan/epidemiologia
15.
Mol Med Rep ; 17(3): 4138-4144, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29257348

RESUMO

Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in the progression of respiratory syncytial virus (RSV) infection remains to be elucidated. The present study quantified the expression level of MEG3 in the nasopharyngeal (NPA) samples of RSV­infected patients and in BEAS­2B cells infected with RSV. The findings of the present study demonstrated that the expression level of lncRNA MEG3 was reduced in the NPA samples of RSV­infected patients and in BEAS­2B cells infected with RSV. In vitro transfection revealed increased mRNA expression levels of toll­like receptor 4 (TLR4), tumor necrosis factor­α (TNFα) and interleukin (IL)­8 following RSV infection in BEAS­2B cells. Additionally, ectopic expression of MEG3 reduced the expression level of TLR4, subsequently suppressing the mRNA expression levels of TNFα and IL­8, indicating the protective role of MEG3 in the process of RSV infection. It is of note, that RSV infection­induced p38 mitogen activated protein kinase (MAPK) and nuclear factor­κB (NF­κB) activation was partly abolished by overexpression of MEG3. In conclusion, to the best of our knowledge, the present study provided the first evidence that lncRNA MEG3 expression level was reduced in the NPA samples of patients with RSV infection and RSV­infected cells. Additionally, it was demonstrated that MEG3 protected human airway epithelial cells from RSV infection, primarily by suppressing TLR4­dependent p38 MAPK and NF­κB signaling.


Assuntos
Bronquiolite Viral/genética , Interações Hospedeiro-Patógeno , NF-kappa B/genética , RNA Longo não Codificante/genética , Infecções por Vírus Respiratório Sincicial/genética , Receptor 4 Toll-Like/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Bronquiolite Viral/imunologia , Bronquiolite Viral/virologia , Linhagem Celular , Criança , Pré-Escolar , Células Epiteliais/imunologia , Células Epiteliais/virologia , Feminino , Regulação da Expressão Gênica , Humanos , Interleucina-8/genética , Interleucina-8/imunologia , Tempo de Internação , Masculino , NF-kappa B/imunologia , Nasofaringe/imunologia , Nasofaringe/virologia , RNA Longo não Codificante/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/crescimento & desenvolvimento , Vírus Sinciciais Respiratórios/imunologia , Transdução de Sinais , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
16.
J Infect Dis ; 217(1): 24-34, 2017 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-29045741

RESUMO

Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles. Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes. Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes. Conclusions: RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.


Assuntos
Bronquiolite Viral/patologia , Bronquiolite Viral/virologia , Genótipo , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/imunologia , Bronquiolite Viral/imunologia , Feminino , Perfilação da Expressão Gênica , Variação Genética , Técnicas de Genotipagem , Hospitalização , Humanos , Lactente , Interferons/metabolismo , Tempo de Internação , Masculino , Nasofaringe/virologia , Neutrófilos/imunologia , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Índice de Gravidade de Doença , Carga Viral
17.
J Pediatr (Rio J) ; 93 Suppl 1: 75-83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28859915

RESUMO

OBJECTIVE: The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. SOURCES: A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: "bronchiolitis, viral," "diagnosis," "epidemiology," "etiology," "therapy," "virology," "prevention and control," "respiratory syncytial virus, human." Additional filters were used. SUMMARY OF FINDINGS: Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future. CONCLUSION: A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes.


Assuntos
Bronquiolite Viral/terapia , Bronquiolite Viral/virologia , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sincicial Respiratório Humano , Doença Aguda , Humanos , Recém-Nascido
18.
Medicine (Baltimore) ; 96(18): e6787, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28471975

RESUMO

Much attention has recently been focused on thymic stromal lymphopoietin (TSLP), IL-33, and periostin in allergic disease, but less is known about their role in viral bronchiolitis.The aim of the study was to investigate whether infants exhibit enhanced nasal airway secretion of TSLP, IL-33, and periostin during natural respiratory viral bronchiolitis compared to healthy controls.In total, 213 infants < 2 years of age, hospitalized with bronchiolitis from October/2013 to April/2016 were enrolled alongside 45 healthy infants. Nasopharyngeal aspirates (NPA) were screened for respiratory viruses by the polymerase chain reaction. TSLP, IL-33, and periostin were measured in NPAs. Clinical data were recorded.At least 1 virus was detected in 186 (87.3%) hospitalized infants: 149 (70%) respiratory syncytial virus (RSV); 42 (19.7%) rhinovirus (HRV); 16 (7.5%) parainfluenza virus (PIV); 9 (4.2%) adenovirus; 10 (4.7%) bocavirus; and 7 (3.3%) metapneumovirus (hMPV). Infants with bronchiolitis had higher levels of TSLP (P = .02), IL-33 (P<.001), and periostin (P = .003) than healthy controls.Detectable levels of TSLP and periostin were more frequent in virus-positive than in virus-negative patients (P = .05). TSLP and IL-33 were also more common in coinfections, mainly RSV and HRV, than in single-infections (P < .05). No patient with bronchiolitis but with negative viral detection had detectable levels of nasal TSLP or IL-33. Infants with hospital stay ≥5 days were more likely to have detectable levels of nasal TSLP and periostin after adjusting by age (P = .01).Bronchiolitis by common respiratory viruses is associated with elevated nasal levels of TSLP, IL-33, and periostin, factors known to be important in the development of Th2-response. Respiratory viruses in early life might shift immune responses toward Th2, involving asthma, and allergic diseases.


Assuntos
Bronquiolite Viral/metabolismo , Moléculas de Adesão Celular/metabolismo , Citocinas/metabolismo , Interleucina-33/metabolismo , Nasofaringe/metabolismo , Bronquiolite Viral/terapia , Bronquiolite Viral/virologia , Estudos Transversais , Feminino , Hospitalização , Humanos , Lactente , Interferon gama/metabolismo , Interleucina-10/metabolismo , Masculino , Nasofaringe/virologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Índice de Gravidade de Doença
19.
Georgian Med News ; (264): 43-50, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28480848

RESUMO

Bronchiolitis is a common condition in children less than 2 years of age and is a leading cause of infant hospitalization. Acute bronchiolitis is characterized by acute wheezing in infants or children and is associated with signs or symptoms of respiratory infection; the most common etiologic agent is respiratory syncytial virus. There is a lack of consensus regarding the clinical definition of acute viral bronchiolitis in children and hence the management varies across the globe. Usually it does not require investigation, treatment is merely supportive and a conservative approach seems adequate in the majority of children, especially for the youngest ones. Managing bronchiolitis, both in the outpatient and inpatient setting remains a challenge to the treating pediatrician. Several recent evidence-based reviews have suggested that bronchodilators or corticosteroids lack efficacy in bronchiolitis and should not be routinely used. The cornerstones of the management of viral bronchiolitis are the administration of oxygen and appropriate fluid therapy, and overall a "minimal handling approach" is recommended. Inhaled adrenaline is commonly used in some countries, but the evidences are sparse. Recently, inhalation with hypertonic saline has been suggested as an optional treatment. When medical treatment fails to stabilize the infants, non-invasive and invasive ventilation may be necessary to prevent respiratory failure. The key to reducing the morbidity and mortality in children with RSV bronchiolitis is through prevention of infection through immunoprophylaxis especially in high-risk children. This review focuses on the epidemiological, clinical, radiographic, and pathologic characteristics, as well as the recent advances in management of acute bronchiolitis.


Assuntos
Antivirais/uso terapêutico , Bronquiolite Viral , Doença Aguda , Bronquiolite Viral/epidemiologia , Bronquiolite Viral/terapia , Bronquiolite Viral/virologia , Humanos , Lactente , Recém-Nascido , Vírus Sinciciais Respiratórios
20.
Pediatr Allergy Immunol ; 28(4): 320-331, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28339145

RESUMO

Respiratory syncytial virus (RSV) is the most common agent of severe airway disease in infants and young children. Large epidemiologic studies have demonstrated a clear relationship between RSV infection and subsequent recurrent wheezing and asthma into childhood, thought to be predominantly related to long-term changes in neuroimmune control of airway tone rather than to allergic sensitization. These changes appear to be governed by the severity of the first RSV infection in infancy which in term depends on viral characteristics and load, but perhaps as importantly, on the genetic susceptibility and on the constitutional characteristic of the host. A variety of viral and host factors and their interplay modify the efficiency of the response to infection, including viral replication and the magnitude of structural and functional damage to the respiratory structures, and ultimately the extent, severity, and duration of subsequent wheezing.


Assuntos
Bronquiolite Viral/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/fisiologia , Doenças Respiratórias/imunologia , Adulto , Bronquiolite Viral/epidemiologia , Bronquiolite Viral/virologia , Criança , Comorbidade , Progressão da Doença , Predisposição Genética para Doença , Interações Hospedeiro-Parasita , Humanos , Lactente , Neuroimunomodulação , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/patogenicidade , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/virologia , Carga Viral , Virulência , Replicação Viral
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