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1.
Front Immunol ; 13: 1025796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341332

RESUMO

Dysregulated innate and adaptive immune response to rhinoviral infection plays an important role in the exacerbation or progressive course of chronic rhinosinusitis (CRS). However, few studies have evaluated whether rhinovirus-induced production of anti-viral interferon is deficient or delayed in inflammatory epithelial cells of patients with CRS with nasal polyps. The aim of the present study is to investigate the replication rates of rhinovirus 16 (RV 16), RV16-induced antiviral interferon secretion, and the expression levels of pattern recognition receptors after RV 16 infection or TLR3 stimulation with poly (I: C) in normal and inflammatory epithelial cells. Inflammatory epithelial cells were obtained from CRS patients with nasal polyps and normal epithelial cells were derived from ethmoid sinus mucosa during endoscopic reduction of blowout fracture or uncinate process mucosa of patients with septal deviation. Cultured cells were infected with RV 16 or treated with poly (I: C) for 24, 48, and 72 h. Cells and media were harvested at each time point and used to evaluate RV16 replication rates, the secretion of IFN-ß, -λ1, -λ2, viperin, Mx, and OAS, and the expression levels of TRL3, RIG-I, MDA5, phospho-NFκB, and phospho-IRF3. RV replication rates reached peak levels 48 h after inoculation in both normal and inflammatory epithelial cells and showed no difference between both groups of epithelial cells at any time point. The release of IFN-ß, -λ1, and -λ2 in normal and inflammatory epithelial cells was also strongly induced 48 h after RV16 inoculation but reached peak levels 24 h after poly (I: C) treatment. The expression levels of viperin, Mx, OAS, TLR3, RIG-I, MDA5, phospho-NFκB, and phospho-IRF3 showed similar patterns in both groups of epithelial cells. These results suggest that the production of RV16-induced antiviral interferons is not deficient or delayed in inflammatory epithelial cells from CRS patients with nasal polyps.


Assuntos
Pólipos Nasais , Sinusite , Humanos , Rhinovirus , Pólipos Nasais/metabolismo , Receptor 3 Toll-Like/metabolismo , Antivirais/metabolismo , Sinusite/metabolismo , Células Epiteliais , Interferons/metabolismo , Interferon beta/metabolismo , Doença Crônica
2.
Front Immunol ; 13: 1017325, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389820

RESUMO

It has become clear that severe bronchiolitis is a heterogeneous disease; even so, current bronchiolitis management guidelines rely on the one-size-fits-all approach regarding achieving both short-term and chronic outcomes. It has been speculated that the use of molecular markers could guide more effective pharmacological management and achieve the prevention of chronic respiratory sequelae. Existing data suggest that asthma-like treatment (systemic corticosteroids and beta2-agonists) in infants with rhinovirus-induced bronchiolitis is associated with improved short-term and chronic outcomes, but robust data is still lacking. We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane's Library to identify eligible randomized controlled trials to determine the efficacy of a personalized, virus-dependent application of systemic corticosteroids in children with severe bronchiolitis. Twelve studies with heterogeneous methodology were included. The analysis of the available results comparing the respiratory syncytial virus (RSV)-positive and RSV-negative children did not reveal significant differences in the associatons between systemic corticosteroid use in acute episode and duration of hospitalization (short-term outcome). However, this systematic review identified a trend of the positive association between the use of systematic corticosteroids and duration of hospitalization in RSV-negative infants hospitalized with the first episode of bronchiolitis (two studies). This evidence is not conclusive. Taken together, we suggest the design for future studies to assess the respiratory virus type in guiding predictive enrichment approaches in infants presenting with the first episode of bronchiolitis. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020173686.


Assuntos
Bronquiolite , Infecções por Vírus Respiratório Sincicial , Lactente , Criança , Humanos , Bronquiolite/terapia , Bronquiolite/complicações , Sistema Respiratório , Rhinovirus , Corticosteroides/uso terapêutico
3.
J Trop Pediatr ; 68(6)2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36323460

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infections are the leading cause of hospitalization in young children. We assessed the epidemiology, severity, clinical characteristics, molecular profile and genetic factors of RSV infections compared to acute respiratory illness (ARI) caused by other respiratory viruses. METHODS: Prospective cohort study was conducted from 2017 to 2018 with children under 2 years old hospitalized with ARI. Detection of respiratory viruses was carried out using RT-PCR. RSVs were genotyped via nucleotide sequencing, and host interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) were determined using SNP TaqMan® Genotyping Assays. RESULTS: A total of 468 children were included; 288 (61.5%) had an infection by a single virus: 202 (70.1%) cases by RSV followed by rhinovirus 36 (12.5%) and influenza 16 (5.6%). Of the RSV cases, 36% were genotyped with a higher prevalence of RSV B (62.1%). The RSV group presented median age of 2.7 months (1.6-6.8), higher frequency in: intensive care unit admission (p = 0.004), mechanical ventilation use (p = 0.018), wheezing (p < 0.001), antimicrobial use (p < 0.001) and low oxygen saturation (p < 0.001). Prematurity (27.2%) was the most frequent comorbidity. RSV patients without comorbidities demonstrated a higher frequency in the combination of IL28B rs12979860 CT/IL28B rs8099917 TG and IL28B rs12979860 TT/IL28B rs8099917 TT genotypes. Viral coinfection was detected in 27 (5.7%) children, with the most frequent being RSV and rhinovirus (14.2%). CONCLUSIONS: This study highlighted the burden of RSV infection in children under 2 years of age, without comorbidities, with a higher need for pediatric ICU admission. Some IL28B allele combinations had a significant association with RSV frequency of infections.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Criança , Lactente , Pré-Escolar , Predisposição Genética para Doença , Estudos Prospectivos , Vírus Sincicial Respiratório Humano/genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/genética , Índice de Gravidade de Doença , Rhinovirus/genética , Estudos de Coortes , Hospitalização , Infecções Respiratórias/epidemiologia
4.
Viruses ; 14(11)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36366439

RESUMO

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the "common cold" and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae.


Assuntos
Asma , COVID-19 , Doenças Transmissíveis , Infecções por Picornaviridae , Infecções Respiratórias , Criança , Adulto , Humanos , Rhinovirus/genética , COVID-19/prevenção & controle , Distanciamento Físico , Asma/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/complicações , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/prevenção & controle , Infecções por Picornaviridae/complicações
5.
Viruses ; 14(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36366528

RESUMO

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.


Assuntos
Asma , Infecções por Picornaviridae , Humanos , Rhinovirus/fisiologia , Interleucina-33/farmacologia , Mastócitos/metabolismo , Antivirais/farmacologia , Permissividade , Replicação Viral , Células Epiteliais
6.
Viruses ; 14(11)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36366542

RESUMO

Asthma symptoms are often exacerbated by the common-cold-causing rhinovirus (RV). In this study, we characterized the temporal behavior of circulating exosomal microRNAs (ExoMiRNAs) in a longitudinal bi-phasic case-control study of mild asthmatics (n = 12) and matched non-atopic healthy controls (n = 12) inoculated with rhinovirus. We aimed to define clinical and immunologic characteristics associated with differentially expressed (DE) miRNAs. In total, 26 DE ExoMiRNAs, including hsa-let-7f-5p, hsa-let-7a-5p, hsa-miR-122-5p, hsa-miR-101-3p, and hsa-miR-126-3p, were identified between asthmatic and healthy subjects after inoculation with RV. Time series clustering identified a unique Cluster of Upregulated DE ExoMiRNAs with augmenting mean expression and a distinct Cluster of Downregulated DE ExoMiRNAs with mean expression decline in asthmatic subjects upon RV challenge. Notably, the Upregulated Cluster correlated with Th1 and interferon-induced cytokines/chemokines (IFN-γ and IFN-γ-inducible protein-10) and interleukin-10 (IL-10). Conversely, the Downregulated Cluster correlated with IL-13, a Th2 cytokine, pulmonary function measurements (FVC%, FEV1%, and PEF%), and inflammatory biomarkers (FeNO, eosinophil%, and neutrophil%). Key ExoMiRNA-target gene and anti-viral defense mechanisms of the Upregulated and Downregulated Clusters were identified by network and gene enrichment analyses. Our findings provide insight into the regulatory role of ExoMiRNAs in RV-induced asthma.


Assuntos
Asma , MicroRNAs , Humanos , Rhinovirus/genética , Estudos de Casos e Controles , MicroRNAs/genética , MicroRNAs/metabolismo , Asma/genética , Pulmão/metabolismo , Citocinas
7.
Immunol Allergy Clin North Am ; 42(4): 727-741, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36265972

RESUMO

Wheezing is common in childhood, although only a small percentage of these children develop asthma. The child's wheezing phenotype and asthma predictive indices help predict the likelihood of a future asthma diagnosis. Viral infections are common in childhood with most wheezing episodes due to respiratory syncytial virus and rhinovirus. Many treatment options exist for wheezing children including both those who wheeze persistently and those who wheeze intermittently due to viral infections.


Assuntos
Asma , Viroses , Pré-Escolar , Humanos , Sons Respiratórios/etiologia , Rhinovirus , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologia , Viroses/complicações , Viroses/diagnóstico , Viroses/epidemiologia , Vírus Sinciciais Respiratórios
8.
Eur J Clin Microbiol Infect Dis ; 41(12): 1445-1449, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36287292

RESUMO

With the COVID-19 pandemic still ongoing, the annual season of influenza and other respiratory virus epidemics has arrived. Specimens from patients suspected of respiratory viruses infection were collected. Viral detection was performed following RNA extraction and real-time RT-PCR. During the study period, we received and tested a total of 606 specimens. Rhinovirus virus was the viral type most prevalent, detected in 186 (45.47%) specimens. The age range of patients positive for influenza A, influenza A (H1N1), and influenza B was 18 days to 13 years. With female prevalence for this viral type, cough and asthma were the main clinical manifestations presented by this viral type. Our results indicate that rhinoviruses, adenoviruses, metapneumoviruses, and influenza are among the most important agents of ARI in pediatrics. The epidemic period of respiratory infections observed in Goiânia can be useful for planning and implementing some prevention strategies.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções Respiratórias , Vírus , Criança , Humanos , Feminino , Influenza Humana/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Prevalência , Pandemias , Vírus/genética , Rhinovirus/genética
9.
Front Immunol ; 13: 871463, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189239

RESUMO

According to the American Centers for Disease Control and Prevention, people in all age groups catch two or more "colds" per year, at least half of which are caused by human rhinoviruses. Despite decades of effort, there are no vaccines or drugs against rhinovirus infections and even social distancing measures that were effective in reducing the spread of the pandemic coronavirus, SARS-CoV-2, did not reduce the rate of rhinovirus detection. Fortunately, most rhinovirus strains are naturally attenuated in that they are not associated with serious illness, hospitalization or mortality. Instead, rhinoviruses are one of the most frequent viruses found in nasal swabs of asymptomatic, healthy people. Since rhinovirus infections cannot be avoided, a rational approach would be to engineer them for the benefit of their human hosts. Rhinovirus infections naturally induce robust mucosal and serum immune responses to all virus-expressed proteins. Several replication-competent, human rhinovirus vaccine vectors able to express protective antigens for other pathogens have already been designed and tested in animal models. With this strategy, the inevitable common cold would be able to induce immunity not just to a specific rhinovirus serotype but to other more pathogenic respiratory viruses as well. This article reviews existing rhinovirus vaccine vector technology and describes the characteristics that make live-attenuated rhinoviruses attractive vaccine candidates for SARS-CoV-2 and other pathogenic respiratory viruses in the future.


Assuntos
COVID-19 , Resfriado Comum , Animais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Resfriado Comum/prevenção & controle , Humanos , Pandemias/prevenção & controle , Rhinovirus , SARS-CoV-2 , Vacinas Atenuadas
10.
Nutrients ; 14(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36296939

RESUMO

An adequate and balanced supply of nutrients is essential for maintaining health, and an optimal immune response is fast, contained and properly controlled, curbing infections quickly while minimizing damage. Several micronutrients contribute to normal immune function and certain dietary fibers, for example pectic polysaccharides, can play an important role in educating and regulating immune cell responses. The aim of this paper is to elaborate on our initial findings that dietary supplementation with carrot-derived rhamnogalacturonan-I (cRG-I) accelerates and augments local innate immune and anti-viral interferon response to a rhinovirus-16 (RV16) infection and reduces the severity and duration of symptoms in humans. Dietary intake of cRG-I also enhanced immune responses to this respiratory viral infection as measured by ex vivo stimulation of whole blood with the Toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid and NK cell function. Consumption of cRG-I also reduced the negative effects of this common cold infection on quality of life as assessed by individual symptom scores. RG-I from carrot is a safe, sustainable, and economically viable solution that could easily be integrated into food products and dietary supplements aiming to support immune fitness and wellbeing.


Assuntos
Daucus carota , Rhinovirus , Humanos , Receptor 3 Toll-Like , Qualidade de Vida , Ramnogalacturonanos , Voluntários Saudáveis , Ligantes , Micronutrientes , Suplementos Nutricionais , Poli I-C , Imunidade , Interferons , Fibras na Dieta
11.
Viruses ; 14(10)2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36298792

RESUMO

Human rhinoviruses (HRVs) are small non-enveloped RNA viruses that belong to the Enterovirus genus within the Picornaviridae family and are known for causing the common cold. Though symptoms are generally mild in healthy individuals, the economic burden associated with HRV infection is significant. A vaccine could prevent disease. The Vero-cell-based viral vaccine platform technology was considered for such vaccine development. Unfortunately, most HRV strains are unable to propagate on Vero cells due to a lack of the major receptor of HRV group A and B, intercellular adhesion molecule (ICAM1, also known as CD54). Therefore, stable human ICAM1 expressing Vero cell clones were generated by transfecting the ICAM1 gene in Vero cells and selecting clones that overexpressed ICAM1 on the cell surface. Cell banks were made and expression of ICAM1 was stable for at least 30 passages. The Vero_ICAM1 cells and parental Vero cells were infected with four HRV prototypes, B14, A16, B37 and A57. Replication of all four viruses was detected in Vero_ICAM1, but not in the parental Vero cells. Altogether, Vero cells expressing ICAM1 could efficiently propagate the tested HRV strains. Therefore, ICAM1-expressing cells could be a useful tool for the development and future production of polyvalent HRV vaccines or other viruses that use ICAM1 as a receptor.


Assuntos
Molécula 1 de Adesão Intercelular , Infecções por Picornaviridae , Rhinovirus , Células Vero , Vacinas Virais , Animais , Humanos , Chlorocebus aethiops , Enterovirus/genética , Enterovirus/imunologia , Infecções por Enterovirus/genética , Infecções por Enterovirus/imunologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/imunologia , Rhinovirus/genética , Rhinovirus/imunologia , Células Vero/imunologia , Vacinas Virais/imunologia
12.
MMWR Morb Mortal Wkly Rep ; 71(40): 1265-1270, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36201400

RESUMO

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.


Assuntos
Asma , COVID-19 , Enterovirus Humano D , Infecções por Enterovirus , Mielite , Infecções Respiratórias , Adolescente , Asma/epidemiologia , Viroses do Sistema Nervoso Central , Criança , Surtos de Doenças , Infecções por Enterovirus/epidemiologia , Humanos , Mielite/epidemiologia , Doenças Neuromusculares , Infecções Respiratórias/epidemiologia , Rhinovirus , Estados Unidos/epidemiologia
13.
Sci Data ; 9(1): 610, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209289

RESUMO

Viruses are genetically and structurally diverse, and outnumber cells by orders of magnitude. They can cause acute and chronic infections, suppress, or exacerbate immunity, or dysregulate survival and growth of cells. To identify chemical agents with pro- or antiviral effects we conducted arrayed high-content image-based multi-cycle infection screens of 1,280 mainly FDA-approved compounds with three human viruses, rhinovirus (RV), influenza A virus (IAV), and herpes simplex virus (HSV) differing in genome organization, composition, presence of an envelope, and tropism. Based on Z'-factors assessing screening quality and Z-scores ranking individual compounds, we identified potent inhibitors and enhancers of infection: the RNA mutagen 5-Azacytidine against RV-A16; the broad-spectrum antimycotic drug Clotrimazole inhibiting IAV-WSN; the chemotherapeutic agent Raltitrexed blocking HSV-1; and Clobetasol enhancing HSV-1. Remarkably, the topical antiseptic compound Aminacrine, which is clinically used against bacterial and fungal agents, inhibited all three viruses. Our data underscore the versatility and potency of image-based, full cycle virus propagation assays in cell-based screenings for antiviral agents.


Assuntos
Anti-Infecciosos Locais , Herpes Simples , Vírus da Influenza A , Aminacrina/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Antivirais/farmacologia , Azacitidina/uso terapêutico , Clobetasol/uso terapêutico , Clotrimazol/uso terapêutico , Herpes Simples/tratamento farmacológico , Humanos , Mutagênicos/uso terapêutico , Rhinovirus
14.
Viruses ; 14(9)2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-36146664

RESUMO

Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite important evidence on the role of RV reported by clinicians and life scientists, there are still unanswered questions regarding their influence on asthma exacerbation in young patients. Thus, we measured the RVspecies-specific IgG titers in our German pediatric exacerbation cohort using a microarray-based technology. For this approach, human sera of patients with exacerbated asthma and wheeze, as well as healthy control subjects (n = 136) were included, and correlation analyses were performed. Concordantly with previously published results, we observed significantly higher cumulative levels of RV species A-specific IgG (p = 0.011) and RV-C-specific IgG (p = 0.051) in exacerbated asthma group compared to age-matched controls. Moreover, atopic wheezers had increased RV-specific IgG levels for species A (p = 0.0011) and species C (p = 0.0009) compared to non-atopic wheezers. Hypothesizing that bacterial infection positively correlates with immune memory against RV, we included nasopharyngeal swab results in our analyses and detected limited correlations. Interestingly, the eosinophil blood titer positively correlated with RV-specific IgG levels. With these observations, we add important observations to the existing data regarding exacerbation in pediatric and adolescent medicine. We propose that scientists and clinicians should pay more attention to the relevance of RV species in susceptible pediatric patients.


Assuntos
Asma , Infecções por Enterovirus , Infecções por Picornaviridae , Adolescente , Formação de Anticorpos , Criança , Infecções por Enterovirus/complicações , Humanos , Imunoglobulina G , Rhinovirus
15.
PLoS One ; 17(9): e0273697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36054088

RESUMO

BACKGROUND: Severe acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses to adult SARI is relatively understudied in Asia. We aimed to determine viral aetiology of adult SARI patients in Kuala Lumpur, Malaysia. METHODS: The prevalence of 20 common (mainly viral) respiratory pathogens, and MERS-CoV, SARS-CoV and 5 bacterial select agents was investigated from May 2017 to October 2019 in 489 SARI adult patients in Kuala Lumpur, Malaysia, using molecular assays (Luminex NxTAG-RPP kit and qPCR assays). Viral metagenomics analysis was performed on 105 negative samples. RESULTS: Viral respiratory pathogens were detected by PCR in 279 cases (57.1%), including 10 (2.0%) additional detections by metagenomics analysis. The most detected viruses were rhinovirus/enterovirus (RV/EV) (49.1%) and influenza virus (7.4%). Three melioidosis cases were detected but no SARS-CoV, MERS-CoV or other bacterial select agents. Bacterial/viral co-detections and viral co-detections were found in 44 (9.0%) and 27 (5.5%) cases respectively, mostly involving RV/EV. Independent predictors of critical disease were male gender, chronic lung disease, lack of runny nose and positive blood culture with a significant bacterial pathogen. Asthma and sore throat were associated with increased risk of RV/EV detection, while among RV/EV cases, males and those with neurological disease were at increased risk of critical disease. CONCLUSIONS: Prior to the COVID-19 pandemic, the high prevalence of respiratory viruses in adults with SARI was mainly attributed to RV/EV. Continued surveillance of respiratory virus trends contributes to effective diagnostic, prevention, and treatment strategies.


Assuntos
COVID-19 , Enterovirus , Infecções Respiratórias , Vírus , Adulto , COVID-19/epidemiologia , Enterovirus/genética , Feminino , Humanos , Malásia/epidemiologia , Masculino , Pandemias , Reação em Cadeia da Polimerase em Tempo Real , Rhinovirus/genética , Vírus/genética
16.
J Med Virol ; 94(12): 5904-5915, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35918790

RESUMO

Rhinovirus (RV)-specific surveillance studies in the Middle East are limited. Therefore, we aimed to study the clinical characteristics, outcomes, and seasonality of RV-associated acute respiratory infection among hospitalized young children in Jordan. We conducted a prospective viral surveillance study and enrolled children <2 years old admitted to a large public hospital in Amman, Jordan (2010-2013). Demographic and clinical data were collected by structured interviews and chart abstractions. Nasal and/or throat swabs were collected and tested for a panel of respiratory viruses, and RV genotyping and speciation was performed. At least one virus was detected in 2641/3168 children (83.4%). RV was the second most common virus detected (n = 1238; 46.9%) and was codetected with another respiratory virus in 730 cases (59.0%). Children with RV codetection were more likely than those with RV-only detection to have respiratory distress but had similar outcomes. RV-A accounted for about half of RV-positive cases (54.7%), while children with RV-C had a higher frequency of wheezing and reactive airway disease. RV was detected year-round and peaked during winter. In conclusion, though children with RV codetection had worse clinical findings, neither codetection nor species affected most clinical outcomes.


Assuntos
Infecções por Enterovirus , Infecções por Picornaviridae , Infecções Respiratórias , Vírus , Criança , Criança Hospitalizada , Pré-Escolar , Humanos , Lactente , Jordânia/epidemiologia , Estudos Prospectivos , Sons Respiratórios , Infecções Respiratórias/epidemiologia , Rhinovirus/genética
17.
Am J Physiol Lung Cell Mol Physiol ; 323(4): L495-L502, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36041223

RESUMO

Primary bronchial epithelial cells (pBECs) obtained from donors have limited proliferation capacity. Recently, conditional reprogramming (CR) technique has overcome this and has provided the potential for extended passaging and subsequent differentiation of cells at air-liquid interface (ALI). However, there has been no donor-specific comparison of cell morphology, baseline gene expression, barrier function, and antiviral responses compared with their "parent" pBECs, especially cells obtained from donors with asthma. We, therefore, collected and differentiated pBECs at ALI from mild donors with asthma (n = 6) for the parent group. The same cells were conditionally reprogrammed and later differentiated at ALI. Barrier function was measured during the differentiation phase. Morphology and baseline gene expression were compared at terminal differentiation. Viral replication kinetics and antiviral responses were assessed following rhinovirus (RV) infection over 96 h. Barrier function during the differentiation phase and cell structural morphology at terminal differentiation appear similar in both parent and CR groups, however, there were elongated cell structures superficial to basal cells and significantly lower FOXJ1 expression in CR group. IFN gene expression was also significantly lower in CR group compared with parent asthma group following RV infection. The CR technique is a beneficial tool to proliferate pBECs over extended passages. Considering lower FOXJ1 expression, viral replication kinetics and antiviral responses, a cautious approach should be taken while choosing CR cells for experiments. In addition, as lab-to-lab cell culture techniques vary, the most appropriate technique must be utilized to best match individual cell functions and morphologies to address specific research questions and experimental reproducibility across the labs.


Assuntos
Asma , Infecções por Picornaviridae , Antivirais/metabolismo , Asma/metabolismo , Células Cultivadas , Células Epiteliais/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Reprodutibilidade dos Testes , Rhinovirus/fisiologia
18.
Viruses ; 14(8)2022 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-36016451

RESUMO

Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in pediatric patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of pediatric RV infections. In total, the respiratory specimens of 776 patients (<18 years), collected from 2013 to 2017, were analyzed. Infections occurred throughout the entire year, with peaks occurring in fall and winter, and showed remarkably high intra- and interseasonal diversity for RV genotypes. RV species were detected in the following frequencies: 49.1% RV-A, 5.9% RV-B, and 43.6% RV-C. RV-C was found to be more frequently associated with asthma (p = 0.04) and bronchiolitis (p < 0.001), while RV-A was more frequently associated with fever (p = 0.001) and pneumonia (p = 0.002). Additionally, 35.3% of the patients had co-infections with other pathogens, which were associated with a longer hospital stay (p < 0.001), need for ventilation (p < 0.001), and pneumonia (p < 0.001). Taken together, this study shows pronounced RV genetic diversity in pediatric patients and indicates differences in RV-associated pathologies, as well as an important role for co-infections.


Assuntos
Coinfecção , Enterovirus , Infecções por Picornaviridae , Infecções Respiratórias , Criança , Enterovirus/genética , Humanos , Epidemiologia Molecular , Infecções Respiratórias/epidemiologia , Rhinovirus/genética , Centros de Atenção Terciária
19.
APMIS ; 130(11): 678-685, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35959516

RESUMO

Vascular endothelium is a semi-permeable barrier that regulates the flow of nutrients, ions, cytokines and immune cells between blood and tissues. Barrier properties of endothelium, its ability to regenerate and the potential for secretion of inflammatory mediators play a crucial role in maintaining local tissue homeostasis. The lung vascular endothelial cells were shown to be infected by human rhinovirus (HRV) and generate antiviral, inflammatory and cytopathic responses. The current study reveals that in the long-time manner, the lung vascular endothelium may efficiently limit the HRV replication via the IFN-dependent 2'-5'-oligoadenylate synthetase 1 activation. This leads to the restoration of integrity accompanied by the up-regulation of adherens and tight junctions, increase of metabolic activity and proliferation rate. Secondly, HRV16-infected cells show delayed and transient up-regulation of the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor, angiopoietin 1 and 2, and neuropilin-1, as well as VEGF receptors. The lung vascular endothelium infected with HRV may limit the infection, recover in time, and regain barrier properties and metabolic functions, thus leading to the restoration of integrated barrier tissue.


Assuntos
Rhinovirus , Fator A de Crescimento do Endotélio Vascular , 2',5'-Oligoadenilato Sintetase , Angiopoietina-1/metabolismo , Antivirais , Citocinas/metabolismo , Células Endoteliais , Endotélio Vascular , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interferons , Pulmão , Neuropilina-1/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Replicação Viral
20.
J Infect ; 85(4): 405-411, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948110

RESUMO

OBJECTIVES: Knowledge of Acute Respiratory virus Infection (ARI) is limited in relation to their substantial global burden. We completed a feasibility study of a novel method to study the natural transmission of respiratory viruses from young children to adults in hospital. METHODS: Between September 2012 and May 2015, we recruited healthy adults (contacts) and paediatric inpatients with ARIs (index) presenting to the University Hospitals Leicester NHS Trust, Leicester, UK. We took nose and throat swabs from all participants prior to controlled, 30 minute interactions between the children with ARIs and adult contacts. Contacts recorded symptoms and provided four nose and throat swabs over ten days post-interaction, which were tested for a panel of respiratory viruses to assess transmission. RESULTS: 111 interactions occurred between children with ARIs and adult contacts. Respiratory viruses were detected in 103 of 111 children (93%), most commonly rhinoviruses (RVs) (67 of 103, 65%). Transmission to an adult contact occurred in 15 (14·6%) of 103 interactions and was inversely associated with the contact being male (adjusted OR 0·12; 95% CI 0·02-0·72). CONCLUSION: Using a novel methodology, we found that natural transmission of ARIs occurred in 15% of an infected child's contacts following a 30 minute interaction, primarily by RVs and when the contact was female. Our model has key advantages in comparison with human challenge studies making it well-suited for further studies of respiratory virus transmission, disease pathogenesis, and clinical and public health interventions to interrupt transmission.


Assuntos
Infecções Respiratórias , Viroses , Vírus , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Rhinovirus
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