RSV vs. rhinovirus bronchiolitis: difference in nasal airway microRNA profiles and NFκB signaling

Hasegawa, Kohei; Pérez‐Losada, Marcos; Hoptay, Claire E.; Epstein, Samuel B.; Mansbach, Jonathan M.; Teach, Stephen J.; Piedra, Pedro A.; Camargo, Carlos A.; Freishtat, Robert J.

doi:10.1038/pr.2017.309

Cited by 41 publications

(47 citation statements)

References 44 publications

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“…However, several recent studies demonstrate the heterogeneity of bronchiolitis by infecting virus. For example, research has shown that RSV and RV infection are associated with differential acute (eg, disease severity) 5 and chronic (eg, incident asthma) 6,7 morbidity burdens, host response (through transcriptomics, 8,9 cytokines, 10 and metabolomics 11,12 ), and airway microbiome profiles 9,13,14 . Despite the clinical and research relevance, it remains unclear how different viruses (including RV species) systemically contribute to downstream molecules that influence clinical outcomes in infants with bronchiolitis.…”

Section: Introductionmentioning

confidence: 99%

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Fujiogi

Camargo

Raita

et al. 2020

Pediatric Allergy Immunology

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Background: Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology. Methods: In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes. Results: In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (P permutation < 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI: 1.05-2.15). In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI: 0.28-0.78). Conclusion: Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.

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Section: Introductionmentioning

confidence: 99%

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Fujiogi

Camargo

Raita

et al. 2020

Pediatric Allergy Immunology

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“…Thus, the high IFN‐levels in the RSV‐positive group may also be due to the presence of extrinsic regulatory factors present in the mucosa of the respiratory tract of infants. For instance, previous studies have shown that the cytokine profile, host transcriptome, microRNAs and the microbiota composition of the airways of infants are quite different during RSV infection relative to other viruses 45,46 . Given the new evidence presented in our study that IFN‐lambda production in human infant AECs can be regulated by pro‐inflammatory signals (eg, IL1β), it is possible that the high levels of IFN lambda during RSV infection are a secondary effect arising from primary dissimilarities in the immune responses against RSV relative to other viruses.…”

Section: Discussionmentioning

confidence: 72%

Innate IFN‐lambda responses to dsRNA in the human infant airway epithelium and clinical regulatory factors during viral respiratory infections in early life

Salka

Arroyo

Chorvinsky

et al. 2020

Clin Experimental Allergy

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Introduction IFN lambda (type III‐IFN‐λ1) is a molecule primarily produced by epithelial cells that provides an important first‐line defence against viral respiratory infections and has been linked to the pathogenesis of viral‐induced wheezing in early life. The goal of this study was to better understand the regulation of innate IFN‐lambda responses in vitro in primary human infant airway epithelial cells (AECs) and in vivo using nasal aspirates during viral respiratory infections. Methods IFN‐lambda protein levels were quantified: (a) in human infant AECs exposed to (poly(I:C) dsRNA) under different experimental conditions (n = 8 donors); and (b) in nasal aspirates of young children (≤3 years) hospitalized with viral respiratory infection (n = 138) and in uninfected controls (n = 74). In vivo IFN‐lambda airway levels during viral infections were correlated with individual characteristics and respiratory disease parameters. Results Our in vitro experiments showed that the poly(I:C)‐induced innate production of IFN lambda in human infant AECs is regulated by (a) p38‐MAPK/NF‐kB dependent mechanism; and (b) exposure to pro‐inflammatory signals such as IL1β. Our in vivo studies demonstrated that (a) infants (<18 months) had higher virus‐induced IFN‐lambda airway secretion; (b) subjects with RSV infection showed the highest IFN‐lambda airway levels; and (c) individuals with the highest virus‐induced IFN‐lambda levels (>90th percentile) had higher viral loads and were more likely to have respiratory sick visits within 12 months of discharge (OR = 5.8). Conclusion IFN‐lambda responses to dsRNA in the human infant airway epithelium are regulated by p38‐MAPK and NF‐kB signalling. High in vivo IFN‐lambda production is influenced by virus type and associated with recurrent respiratory sick visits in young children.

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“…Conversely, miR-22 was shown to be suppressed in asthmatic epithelium in IFV infection which lead to aberrant epithelial response, contributing to exacerbations (Moheimani et al, 2018). Other than these direct evidence of miRNA changes in contributing to exacerbations, an increased number of miRNAs and other non-coding RNAs responsible for immune modulation are found to be altered following viral infections (Globinska et al, 2014;Feng et al, 2018;Hasegawa et al, 2018). Hence non-coding RNAs also presents as targets to modulate viral induced airway changes as a means of managing exacerbation of chronic airway inflammatory diseases.…”

Section: Mirna and Other Epigenetic Modulation Of Inflammationmentioning

confidence: 99%

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

Tan

Lim

Liu

et al. 2020

Front. Cell Dev. Biol.

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Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.

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RSV vs. rhinovirus bronchiolitis: difference in nasal airway microRNA profiles and NFκB signaling

Cited by 41 publications

References 44 publications

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

Innate IFN‐lambda responses to dsRNA in the human infant airway epithelium and clinical regulatory factors during viral respiratory infections in early life

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

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