Similar Frequency of Rhinovirus‐Infectible Cells in Upper and Lower Airway Epithelium

Mosser, Anne G.; Brockman-Schneider, Rebecca; Amineva, S. P.; Burchell, Lacinda; Sedgwick, Julie B.; Busse, William W.; Gern, James E.

doi:10.1086/339339

Cited by 158 publications

(150 citation statements)

References 28 publications

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“…The HRV strains induced pronounced CPE in stationary RD cell cultures following incubation at 36 u C, which substantially differs from the traditional isolation practice for HRV (incubation in rolling HeLa Ohio cells at 33 u C). The effective replication of some HRV prototype strains at 36 u C, which is the temperature in lower airways, has also been described previously (Mosser et al, 2002;Papadopoulos et al, 1999;Puro et al, 2005). The isolation of only HRV strains that genetically belonged to the minor receptor group may be explained by the selectivity of the RD cell line.…”

Section: Discussionmentioning

confidence: 55%

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

Blomqvist

Savolainen-Kopra

Paananen

et al. 2009

Journal of General Virology

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Human rhinoviruses (HRVs), which are the most frequent causative agents of acute upper respiratory tract infections, are abundant worldwide. We have identified HRV strains in environmental specimens collected in Finland, Latvia and Slovakia during the surveillance of polioand other enteroviruses. These acid-sensitive HRV strains were isolated under conditions optimized for growth of most of the enteroviruses, i.e. in stationary human rhabdomyosarcoma cells incubated at 36 6C. Phylogenetic analysis of the sequences derived from the partial 59 noncoding region and the capsid region coding for proteins VP4/VP2 and VP1 showed that the HRV field strains clustered together with prototype strains of the HRV minor receptor group. Partial sequences of the 3D polymerase coding region generally followed this pattern, with the exception of a set of three HRV field strains that formed a subcluster not close to any of the established HRV-A types, suggesting that recombination may have occurred during evolution of these HRV strains. Phylogenetic analysis of the VP4/VP2 capsid protein coding region showed that the 'environmental' HRV field strains were practically identical to HRV strains recently sequenced by others in Australia, the United States and Japan. Analysis of amino acids corresponding to the intercellular adhesion molecule-1 receptor footprint in major receptor group HRVs and also in the low-density lipoprotein receptor footprint of minor receptor group HRVs showed conservation of the 'minor receptor group-like' amino acids, indicating that the field strains may have maintained their minor receptor group specificity. INTRODUCTIONHuman rhinoviruses (HRVs) belong to the family Picornaviridae and together with human enteroviruses (HEV) and a number of non-human enterovirus strains comprise the largest genus (Enterovirus) in the family (Knowles, 2008). Clinical illnesses caused by HRV are typically mild and self-limiting upper respiratory tract infections or common colds, but HRVs have also been increasingly associated with other clinical consequences of respiratory tract infection such as acute otitis media (NoksoKoivisto et al., 2004;Pitkaranta et al., 1998;Vesa et al., 2001), acute community-acquired sinusitis (Pitkaranta et al., 1997(Pitkaranta et al., , 2001), bronchiolitis (Hayden, 2004), pneumonia (Papadopoulos, 2004 and exacerbations of existing respiratory disorders such as asthma (Gern, 2002) and chronic obstructive pulmonary disease (Greenberg, 2002).HRV encompasses 100 designated serotypes, including two antigenically distinct subtypes of serotype HRV1 (HRV1A and HRV1B) (Hamparian et al., 1987;Kapikian et al., 1967Kapikian et al., , 1971. The current taxonomy is based on genetic relationships of HRV. Genetic analysis of VP4/VP2 (Savolainen et al., 2002a) and VP1 (Laine et al., 2005; Ledford et al., 2004) capsid protein coding regions showed that the 100 serotypes cluster into two genetically distinct species, HRV-A and HRV-B. One HRV strain originally assigned as HRV87 belongs to the enterovirus species H...

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Section: Discussionmentioning

confidence: 55%

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

Blomqvist

Savolainen-Kopra

Paananen

et al. 2009

Journal of General Virology

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“…However, we have shown viral replication and IFN responses in response to RV infection. Also, we believe the distinct nature of human RV infection, which causes minimal cytotoxicity (36,37) and infects relatively few cells in the airway compared with other respiratory viruses (38)(39)(40), argues in favor of the RV model despite the relatively low levels of replication. Another potential concern relates to its dependence on minor group viruses.…”

Section: Original Researchmentioning

confidence: 94%

Rhinovirus Infection Induces Interleukin-13 Production from CD11b-Positive, M2-Polarized Exudative Macrophages

Chung¹,

Hong

Lei³

et al. 2015

Am J Respir Cell Mol Biol

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Rhinovirus (RV) causes asthma exacerbations. Previously, we showed that adherent bronchoalveolar cells from allergen-treated mice produce IL-13 when stimulated with RV ex vivo, implicating cells of the monocyte/macrophage lineage in viral-induced airway inflammation. In this study, we hypothesized that RV infection of allergen-treated mice results in IL-13 production by CD11b1 exudative macrophages in vivo. We sensitized and challenged BALB/c mice with ovalbumin (OVA), after which mice were inoculated with RV or sham HeLa cell lysate. After 1 day, lungs were harvested, and cell suspensions were analyzed by flow cytometry. We repeated this process in IL-13 reporter mice, CD11b-DTR mice in which diphtheria toxin selectively depletes CD11b1 cells, and chemokine receptor 2 (CCR2) null mice. We found that lungs of mice infected with RV alone showed increases in CD451, CD681, F4/801, Ly6C1, and CD11b high cells, indicating an influx of inflammatory monocytes and exudative macrophages. The combination of OVA and RV had synergistic effects on the exudative macrophage number. However, CD11b1 cells from OVA-treated, RV-infected mice showed M2 polarization, including expression of CD206 and CD301 and production of IL-13. Similar results were obtained in IL-13 reporter mice. Diphtheria toxin depleted CD11b1, IL-13-producing cells in OVA-treated, RV-infected, CD11b-DTR mice, decreasing airway inflammation and responsiveness. CD11b1, Ly6C1 cells were reduced in CCR2 knockout mice. We conclude that, in contrast to naive mice, RV infection of mice with allergic airways disease induces an influx of IL-13-producing CD11b1 exudative macrophages bearing M2 macrophage markers. This finding further implicates alternatively activated macrophages in RV-induced asthma exacerbations.

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“…In those with COPD but not in healthy subjects, RV also promotes acquisition of secondary bacterial infections (8,9). These observations indicate that RV, which infects and replicates primarily in airway epithelial cells (10), may impair innate immune functions of airway epithelium in subjects with chronic airway diseases, but the mechanisms are not well understood.…”

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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Similar Frequency of Rhinovirus‐Infectible Cells in Upper and Lower Airway Epithelium

Cited by 158 publications

References 28 publications

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

Rhinovirus Infection Induces Interleukin-13 Production from CD11b-Positive, M2-Polarized Exudative Macrophages

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

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