Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

Bossios, Apostolos; Psarras, Stelios; Gourgiotis, Dimitrios; Skevaki, Chrysanthi; Constantopoulos, A; Saxoni-Papageorgiou, Photini; Papadopoulos, Nikolaos G.

doi:10.1186/1465-9921-6-114

Cited by 74 publications

(84 citation statements)

References 44 publications

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“…In vitro, the different rhinovirus serotypes seem to differ in their cytotoxic capacity, but in most cases cytotoxicity appears to be cell density dependent, i.e. only observed in sparsely seeded cultures exposed to the virus, conditions that are not mimicked in the in vivo situation [88]. Rather than cytotoxic effects, experimental or naturally occurring exposure of airway epithelial cells to HRV normally induces a virus-specific cytopathic effect, which is associated with an inflammatory reaction [89].…”

Section: Hrv Infection and Host Immune Responsementioning

confidence: 99%

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

2014

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There is evidence that respiratory viruses play a key role in the development and exacerbation of obstructive respiratory diseases in children. This review attempts to juxtapose the separate profiles and prototypes of pathogenenetic mechanisms represented by the two most common amongst such viruses: respiratory syncytial virus (RSV) and human rhinovirus (HRV).RSV represents the most common agent of severe airway disease in infants and young children, and is predominant in winter months. Large epidemiological studies have revealed an unequivocal relationship between RSV infection and subsequent wheezing into childhood, thought to be related to long-term changes in neuroimmune control of the airways rather than allergic sensitisation.HRV is a highly diverse group of viruses that affect subjects of all ages, is ubiquitous and occurs yearround. In contrast to RSV, infections with HRV cause minimal cytotoxicity but induce a rapid production of cytokines and chemokines with amplification of the inflammatory response. The susceptibility to HRVinduced bronchiolitis and subsequent wheezing appears to be linked to individual predisposition since it is often associated with a family or personal history of asthma/atopy.Thus, RSV probably serves as an "inducer" rather than a "trigger". Conversely, HRVs seem to serve as a "trigger" rather than an "inducer" in predisposed individuals. @ERSpublications Comprehensive overview of the different roles of RSV and HRV in the pathogenesis of recurrent wheezing in childhood

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Section: Hrv Infection and Host Immune Responsementioning

confidence: 99%

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

2014

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“…RV has also been shown to delay wound closure in nonpolarizedundifferentiated bronchial epithelial cells (14). Furthermore, basal/undifferentiated cells, which are readily accessible after airway epithelial injury and during regeneration, are more susceptible to RV infection than are the suprabasal/differentiated cells (15).…”

Section: Clinical Relevancementioning

confidence: 99%

Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium

Faris¹,

Ganesan²,

Chattoraj³

et al. 2016

Am J Respir Cell Mol Biol

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Rhinovirus (RV), which causes exacerbation in patients with chronic airway diseases, readily infects injured airway epithelium and has been reported to delay wound closure. In this study, we examined the effects of RV on cell repolarization and differentiation in a model of injured/regenerating airway epithelium (polarized, undifferentiated cells). RV causes only a transient barrier disruption in a model of normal (mucociliary-differentiated) airway epithelium. However, in the injury/regeneration model, RV prolongs barrier dysfunction and alters the differentiation of cells. The prolonged barrier dysfunction caused by RV was not a result of excessive cell death but was instead associated with epithelial-to-mesenchymal transition (EMT)-like features, such as reduced expression of the apicolateral junction and polarity complex proteins, E-cadherin, occludin, ZO-1, claudins 1 and 4, and Crumbs3 and increased expression of vimentin, a mesenchymal cell marker. The expression of Snail, a transcriptional repressor of tight and adherence junctions, was also up-regulated in RV-infected injured/regenerating airway epithelium, and inhibition of Snail reversed RV-induced EMT-like features. In addition, compared with sham-infected cells, the RV-infected injured/regenerating airway epithelium showed more goblet cells and fewer ciliated cells. Inhibition of epithelial growth factor receptor promoted repolarization of cells by inhibiting Snail and enhancing expression of E-cadherin, occludin, and Crumbs3 proteins, reduced the number of goblet cells, and increased the number of ciliated cells. Together, these results suggest that RV not only disrupts barrier function, but also interferes with normal renewal of injured/regenerating airway epithelium by inducing EMT-like features and subsequent goblet cell hyperplasia.Keywords: barrier function; epithelial-to-mesenchymal transition; Crumbs polarity complex; epithelial growth factor receptor; goblet cell hyperplasia Clinical RelevanceTo the best of our knowledge, this is the first study to demonstrate that rhinovirus delays cell repolarization in a model of injured/regenerating, but not normal, airway epithelium by inducing epithelial-to-mesenchymal transition-like features. Furthermore, rhinovirus reduces ciliated cell differentiation and promotes goblet-cell differentiation and mucin gene expression. These changes depended partially on persistent EGFR activation induced by rhinovirus. Such changes during regeneration can lead to airway epithelium with impaired barrier and mucociliary clearance functions.Airway epithelium that lines the respiratory tract acts as a physical barrier between the external environment and the lung and plays an important role in maintaining tissue homeostasis. Paracellular permeability of airway epithelium is maintained through the co-operation of two functionally distinct structural components: tight and adherence junctions located in the apicolateral membranes. Tight junctions regulate the transport of solutes and ions across airway epithelium...

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“…Allergens and respiratory viruses act synergistically in the expression of asthma symptoms in adults and children [13,33]. RV-induced epithelial cytotoxicity could increase the penetration and effects of allergens, leading to further induction of inflammation [87,88]. Synergy between virus and mite (Dermatophagoides pteronyssinus antigen 1)-induced inflammation may also occur through combined nuclear factor-kB activation [89].…”

Section: Mechanisms Of Virus-induced Exacerbationmentioning

confidence: 99%

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers

Xepapadaki¹,

Papadopoulos²

2010

European Respiratory Journal

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Respiratory infections have been implicated in the origin and exacerbation of asthma in a variety of ways; however, systemisation of this knowledge in a way helpful for disease management remains suboptimal.Several conceptual issues need to be taken into account: the fact that the effects of an infection may vary according to genetic background, the current immune status of the host, and parallel environmental stimuli, in addition to the particular infectious agent itself. Moreover, childhood is a very special period because of the continuous processes taking place, such as neural, immune and respiratory maturation.Epidemiological studies have convincingly demonstrated that the majority of asthma exacerbations, in both adults and children, follow viral upper respiratory tract infections. Asthma exacerbations are still often unresponsive to current asthma treatment, and new therapeutic approaches are required.This review presents current knowledge on the associations between infection and exacerbation of established asthma with respect to definitions, epidemiology, mechanisms and treatment.

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Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

Cited by 74 publications

References 44 publications

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers

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