Group Rhinovirus Research Articles

Sphingosine Prevents Rhinoviral Infections.

Rhinoviral infections cause approximately 50% of upper respiratory tract infections and novel treatment options are urgently required. We tested the effects of 10 μM to 20 μM sphingosine on the infection of cultured and freshly isolated human cells with minor and major group rhinovirus in vitro. We also performed in vivo studies on mice that were treated with an intranasal application of 10 μL of either a 10 μM or a 100 μM sphingosine prior and after infection with rhinovirus strains 1 and 2 and determined the infection of nasal epithelial cells in the presence or absence of sphingosine. Finally, we determined and characterized a direct binding of sphingosine to rhinovirus. Our data show that treating freshly isolated human nasal epithelial cells with sphingosine prevents infections with rhinovirus strains 2 (minor group) and 14 (major group). Nasal infection of mice with rhinovirus 1b and 2 is prevented by the intranasal application of sphingosine before or as long as 8 h after infection with rhinovirus. Nasal application of the same doses of sphingosine exerts no adverse effects on epithelial cells as determined by hemalaun and TUNEL stainings. The solvent, octylglucopyranoside, was without any effect in vitro and in vivo. Mechanistically, we demonstrate that the positively charged lipid sphingosine binds to negatively charged molecules in the virus, which seems to prevent the infection of epithelial cells. These findings indicate that exogenous sphingosine prevents infections with rhinoviruses, a finding that could be therapeutically exploited. In addition, we demonstrated that sphingosine has no obvious adverse effects on the nasal mucosa. Sphingosine prevents rhinoviral infections by a biophysical mode of action, suggesting that sphingosine could serve to prevent many viral infections of airways and epithelial cells in general. Future studies need to determine the molecular mechanisms of how sphingosine prevents rhinoviral infections and whether sphingosine also prevents infections with other viruses inducing respiratory tract infections. Furthermore, our studies do not provide detailed pharmacokinetics that are definitely required before the further development of sphingosine.

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus-induced first wheezing episode in children.

Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis. Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3-23months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4years. The mean age of the children was 14.3months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p<0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group. Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.

Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course.

Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1β and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group × cytokine interaction was observed in the levels of interferon gamma (IFN-γ), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV.

ELISA-Based Assay for Studying Major and Minor Group Rhinovirus-Receptor Interactions.

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, and the need for preclinical models for the screening of vaccine candidates and antiviral compounds. We report the establishment and characterization of an ELISA-based assay for studying major and minor group RV–receptor interactions. This assay is based on the interaction of purified virus with plate-bound human receptor proteins, intercellular adhesion molecule 1 (ICAM-1), and low density lipoprotein receptor (LDLR). Using RV strain-specific antibodies, we demonstrate the specific binding of a panel of major and minor RV group types including RV-A and RV-B strains to ICAM-1 and LDLR, respectively. We show that the RV–receptor interaction can be blocked with receptor-specific antibodies as well as with soluble receptors and neutralizing RV-specific antibodies. The assay is more sensitive than a cell culture-based virus neutralization test. The ELISA assay will therefore be useful for the preclinical evaluation for preventive and therapeutic strategies targeting the RV–receptor interaction, such as vaccines, antibodies, and anti-viral compounds.

Nasal epithelial cells to assess in vitro immune responses to respiratory virus infection in pregnant women with asthma

Respiratory virus-induced asthma exacerbations occur frequently during pregnancy and are associated with adverse outcomes for mother and child. Primary nasal epithelial cells (pNECs) provide a useful method to study immune responses in pregnancy. pNECs were obtained by nasal brushings from pregnant and non-pregnant women with and without asthma. pNECS were infected in vitro with major group Rhinovirus 43 (RV43) and seasonal influenza (H3N2). Following infection, pNECs showed measurable quantities of interferon (IFN)-λ, IL-1β, IL-8, IP-10 and MIP1-α. pNECs provide a safe and effective method for studying respiratory epithelial cell responses during pregnancy.

Multi‐season analyses of causative pathogens in children hospitalized with asthma exacerbation

BackgroundRespiratory viral and mycoplasma infections are associated with childhood asthma exacerbations. Here, we explored epidemiologic profile of causative pathogens and possible factors for exacerbation in a single center over a three‐year period.MethodsHospitalized asthmatic children with attack aged 6 months‐17 years were recruited between 2012 and 2015 (n = 216). Nasopharyngeal mucosa cell samples were collected from the participants and examined by reverse transcription‐polymerase chain reaction to detect rhinovirus (RV), respiratory syncytial virus (RSV), enterovirus (EV), parainfluenza virus (PIV), Mycoplasma pneumoniae, and others. Clinical features, laboratory data, asthma exacerbation intensity, and asthma severity were compared among participants. Epidemiologic profile of causative pathogens and possible factors for exacerbation were explored.ResultsViruses and/or Mycoplasma pneumoniae were detected in 75% of the participants. Rhinovirus (48%) was the most commonly detected virus in the participants with single infection, followed by RSV (6%). The median age at admission in the RV group was significantly higher than that in the RSV group. Insufficient asthma control and allergen sensitization were significantly related to RV‐associated asthma exacerbation. There was no seasonality of pathogen types associated with asthma exacerbation although a sporadic prevalence of EV‐D68 was observehinovirud. Rhinovirus were repeatedly detected in multiple admission cases.ConclusionOur three‐year analysis revealed that patients with RV infection were significantly prone to repeated RV infection in the subsequent exacerbation and good asthma control could prevent RV‐associated asthma development and exacerbation. Multiple‐year monitoring allowed us to comprehend the profile of virus‐ and/or mycoplasma‐induced asthma exacerbation.

Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells

Human rhinoviruses commonly cause upper respiratory infections, which may be complicated by secondary bacterial infection. Vitamin D replacement reduces risk of acute respiratory infections in vitamin D-deficient individuals, but the mechanisms by which such protection is mediated are incompletely understood. We therefore conducted experiments to characterise the influence of the major circulating metabolite 25-hydroxyvitamin D (25[OH]D) and the active metabolite 1,25-dihydroxyvitamin D (1,25[OH]2D) on responses of a respiratory epithelial cell line (A549 cells) to infection with a major group human rhinovirus (RV-16). Pre-treatment of A549 respiratory epithelial cells with a physiological concentration (10−7M) of 25(OH)D induced transient resistance to infection with RV-16 and attenuated RV-16-induced expression of the genes encoding intercellular adhesion molecule 1 (ICAM-1, a cell surface glycoprotein that acts as the cellular receptor for major group rhinoviruses) and platelet-activating factor receptor (PAFR, a G-protein coupled receptor implicated in adhesion of Streptococcus pneumoniae to respiratory epithelial cells). These effects were associated with enhanced expression of the genes encoding the NF-κB inhibitor IκBα and the antimicrobial peptide cathelicidin LL-37. Our findings suggest possible mechanisms by which vitamin D may enhance resistance to rhinovirus infection and reduce risk of secondary bacterial infection in vitamin D-deficient individuals.

Authorised medicinal product Aspecton® Oral Drops containing thyme extract KMTv24497 shows antiviral activity against viruses which cause respiratory infections

The common cold is a respiratory disease often caused by viral pathogens, including a major group of human rhinoviruses (HRV). Currently, there is no specific antiviral approach available against these viruses. Another viral pathogen that causes respiratory diseases is the influenza virus (IV). Even though a few approved drugs are available for antiviral treatment against IV, these are prone to lose their effectiveness due to the rapid emergence of resistant virus variants. Therefore, new effective approaches characterised by a broad antiviral activity and wide availability would be very advantageous. In this study the authors aimed to investigate the antiviral potential of an authorised medicinal product (Aspecton® Oral Drops) containing a specific thyme extract (KMTv24497) against human rhinovirus serotype 1a (HRV1a), as well as against an influenza A virus isolate of the 2009 pandemic (H1N1pdm09) at non-toxic concentrations. To the best of the authors knowledge, they were able to demonstrate, for the first time, the in vitro antiviral activity of a thyme extract containing an authorised medicinal product in non-toxic concentrations against an HRV, as well as against an influenza A virus strain in cell culture. This study represents a first approach to prove a causal therapeutic effect in addition to the already described symptomatic effects for a thyme preparation. Patients with common cold infections may profit from the additional causal therapeutic effects of an expectorant.

Respiratory viral infections in infancy and school age respiratory outcomes and healthcare costs.

To determine the impact of viral lower respiratory tract infections (LRTIs) in infancy including rhinovirus (RV) and infancy respiratory syncytial virus (RSV), on school age pulmonary function and healthcare utilization in prematurely born children. School age respiratory outcomes would be worse and healthcare utilization greater in children who had viral LRTIs in infancy. Prospective study. A cohort of prematurely born children who had symptomatic LRTIs during infancy documented, was recalled. Pulmonary function was assessed at 5 to 7 years of age and health related costs of care from aged one to follow-up determined. Fifty-one children, median gestational age 33+6 weeks, were assessed at a median (IQR) age 7.03 (6.37-7.26) years. Twenty-one children had no LRTI, 14 RV LRTI, 10 RSV LRTI, and 6 another viral LRTI (other LRTI). Compared to the no LRTI group, the RV group had a lower FEV1 (P = 0.033) and the other LRTI group a lower FVC (P = 0.006). Non-respiratory medication costs were higher in the RV (P = 0.018) and RSV (P = 0.013) groups. Overall respiratory healthcare costs in the RV (£153/year) and RSV (£27/year) groups did not differ significantly from the no LRTI group (£56/year); the other LRTI group (£431/year) had higher respiratory healthcare costs (P = 0.042). In moderately prematurely born children, RV and RSV LRTIs in infancy were not associated with higher respiratory healthcare costs after infancy. Children who experienced LRTIs caused by other respiratory viruses (including RV) had higher respiratory healthcare costs and greater pulmonary function impairment.

Asthma and lung function in adulthood after a viral wheezing episode in early childhood.

Viral aetiology of infection has a significant role in the long-term outcome of early-childhood wheezing. This study examines asthma and lung function in adulthood after early-childhood wheezing induced by respiratory syncytial virus (RSV) and rhinovirus (RV). A total of 100 children were hospitalized for a wheezing episode at less than 24 months of age from 1992 to 1993 in Kuopio University Hospital (Finland). Adenovirus, influenza A and B virus, parainfluenza (1-3) virus, and RSV were tested on admission using antigen detection and antibody assays, and RSV and RV were tested by polymerase chain reaction (PCR). In 2010, 49 cases and 60 population controls attended a follow-up study, which included spirometry with bronchodilation test and fractionally exhaled nitric oxide (FENO ) measurements. Current asthma was present in 64% of the cases with RV-induced wheezing (OR 17.0 [95%CI 3.9-75.3] vs controls), in 43% of the cases with RSV-induced wheezing episode (6.1 [1.5-24.9] vs controls), and in 12% of the controls. The RV group showed significantly higher mean FENO values than the RSV group and controls. RV-positive cases had lower MEF50 before bronchodilation and higher MEF50, FEV1, and FEV1/FVC bronchodilation responses than controls. RSV-positive cases had lower FVC than controls before bronchodilation. Cases with RV- and RSV-induced early-childhood wheezing had increased risk for asthma in adulthood, and RV-positive cases had significantly higher FENO values than RSV-positive cases and controls. Compared to controls, RV-positive cases showed more bronchial reactivity, and RSV-positive cases showed lower FVC before bronchodilation in lung function testing. Children with RV- or RSV-induced wheezing in early childhood have an increased risk for asthma and lung function abnormalities in adulthood.

The suppression of innate immune response by human rhinovirus C

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-β activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.

Respiratory-syncytial-virus- and rhinovirus-related bronchiolitis in children aged

SummaryBackgroundBronchiolitis is the most common reason for hospitalization in young children. In addition to respiratory syncytial virus (RSV), other viruses have been increasingly implicated. Guidance on testing has also changed.AimsTo compare clinicopathological outcomes in young children admitted with bronchiolitis due to RSV in comparison with rhinovirus (RV), and identify associated risk/epidemiological factors.MethodsChildren aged less than two years admitted to hospital with a clinical diagnosis of bronchiolitis with positive results for either RSV or RV were included in this study. Polymerase-chain-reaction-negative cases using an extended respiratory virus panel served as a control group. Retrospective data were collected on sex, risk factors, respiratory support, intravenous fluids and antibiotics. Outcomes such as length of stay (LOS) and need for transfer to the high-dependency unit/paediatric intensive care unit were included.FindingsTwo hundred and twenty-seven out of 437 nasopharyngeal aspirate samples were positive for either RSV (N = 162) or RV (N = 65). The median age of cases was three months and 75% had at least one risk factor. Risk factors were higher in the RV group (P = 0.004). RV accounted for the majority of cases outside the RSV season (P < 0.01). RV-associated bronchiolitis had a longer LOS (more than seven days) (P < 0.05) and increased need for chest X-rays and/or antibiotics (P < 0.05). Use of intravenous fluids and respiratory support were higher in the RV group, but the difference was not significant.ConclusionsRV is the second most common pathogen associated with bronchiolitis and is isolated all year round. This may be important in those with risk factors resulting in prolonged LOS. Further research is necessary to establish the exact role of RV in this common condition, particularly outside the traditional RSV season.

Unexpectedly Higher Morbidity and Mortality of Hospitalized Elderly Patients Associated with Rhinovirus Compared with Influenza Virus Respiratory Tract Infection.

Rhinovirus is a common cause of upper and lower respiratory tract infections in adults, especially among the elderly and immunocompromised. Nevertheless, its clinical characteristics and mortality risks have not been well described. A retrospective analysis on a prospective cohort was conducted in a single teaching hospital center over a one-year period. We compared adult patients hospitalized for pneumonia caused by rhinovirus infection with those hospitalized for influenza infection during the same period. All recruited patients were followed up for at least 3 months up to 15 months. Independent risk factors associated with mortality for rhinovirus infection were identified. Between 1 March 2014 and 28 February 2015, a total of 1946 patients were consecutively included for analysis. Of these, 728 patients were hospitalized for rhinovirus infection and 1218 patients were hospitalized for influenza infection. Significantly more rhinovirus patients were elderly home residents and had chronic lung diseases (p < 0.001), whereas more influenza patients had previous stroke (p = 0.02); otherwise, there were no differences in the Charlson comorbidity indexes between the two groups. More patients in the rhinovirus group developed pneumonia complications (p = 0.03), required oxygen therapy, and had a longer hospitalization period (p < 0.001), whereas more patients in the influenza virus group presented with fever (p < 0.001) and upper respiratory tract symptoms of cough and sore throat (p < 0.001), and developed cardiovascular complications (p < 0.001). The 30-day (p < 0.05), 90-day (p < 0.01), and 1-year (p < 0.01) mortality rate was significantly higher in the rhinovirus group than the influenza virus group. Intensive care unit admission (odds ratio (OR): 9.56; 95% confidence interval (C.I.) 2.17–42.18), elderly home residents (OR: 2.60; 95% C.I. 1.56–4.33), requirement of oxygen therapy during hospitalization (OR: 2.62; 95% C.I. 1.62–4.24), and hemoglobin level <13.3 g/dL upon admission (OR: 2.43; 95% C.I. 1.16–5.12) were independent risk factors associated with 1-year mortality in patients hospitalized for rhinovirus infection. Rhinovirus infection in the adults was associated with significantly higher mortality and longer hospitalization when compared with influenza virus infection. Institutionalized older adults were particularly at risk. More stringent infection control among health care workers in elderly homes could lower the infection rate before an effective vaccine and antiviral become available.

Comparison of cytokine expression profiles in infants with a rhinovirus induced lower respiratory tract infection with or without wheezing: a comparison with respiratory syncytial virus.

PurposeThe aim of this study was to evaluate whether infants with rhinovirus (RV) infection-induced wheezing and those with respiratory syncytial virus (RSV) infection-induced wheezing have different cytokine profiles in the acute stage.MethodsOf the infants with lower respiratory tract infection (LRTI) between September 2011 and May 2012, 88 were confirmed using reverse transcription polymerase chain reaction and hospitalized. Systemic interferon-gamma (IFN-γ), interleukin (IL)-2, IL-12, IL-4, IL-5, IL-13, and Treg-type cytokine (IL-10) responses were examined with multiplex assay using acute phase serum samples.ResultsOf the 88 patients, 38 had an RV infection (RV group) and 50 had an RSV infection (RSV group). In the RV group, the IFN-γ and IL-10 concentrations were higher in the patients with than in the patients without wheezing (P=0.022 and P=0.007, respectively). In the RSV group, the differences in IFN-γ and IL-10 concentrations did not reach statistical significance between the patients with and the patients without wheezing (P=0.105 and P=0.965, respectively). The IFN-γ and IL-10 concentrations were not significantly different between the RV group with wheezing and the RSV group with wheezing (P=0.155 and P=0.801, respectively), in contrast to the significant difference between the RV group without wheezing and the RSV group without wheezing (P=0.019 and P=0.035, respectively).ConclusionIn comparison with RSV-induced LRTI, RV-induced LRTI combined with wheezing showed similar IFN-γ and IL-10 levels, which may have an important regulatory function.

Can the common cold protect you from influenza? A murine model of respiratory viral co-infection.

Abstract Clinical cases demonstrate that up to 30% of respiratory infections involve more than one virus with rhinovirus being one of the most common in co-infections. Interestingly, rhinovirus has been found to exacerbate disease when co-infecting with adenovirus, whereas it can modulate disease when co-infecting with influenza A virus. However, there has yet to be a clear connection for how these viruses interact in the host to alter immune responses and disease severity. We are using a murine model of respiratory viral co-infection to determine how minor group rhinovirus (RV1B) affects pathogenesis during influenza A virus (PR8) infection. BALB/c mice were infected with RV1B or mock-infected two days before infecting with a high (100% lethal) or low (40% lethal) dose of PR8. Mice co-infected with RV1B and low dose PR8 had reduced clinical signs, weight loss and mortality compared to mice infected with PR8 alone. However, RV1B did not reduce disease severity upon infection with a high dose of PR8. Groups of mice were infected with RV1B or mock-infected two days prior to infection with low dose PR8 and were sacrificed 4 and 7 days later to quantify PR8 in the lungs. Single- and co-infected mice had similar PR8 titers on day 4; however, the co-infected group completely cleared PR8 on day 7 while the single infected group still had detectable titers. These results suggest that rhinovirus stimulates an immune response that promotes viral clearance and recovery upon infection with influenza A virus. Ongoing work will characterize this response to explain how respiratory viral co-infections can manipulate host immune responses to change disease outcome.

Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM-1 levels and endosomal acidification and is inhibited by L-carbocisteine.

Increased viral replication and cytokine production may be associated with the pathogenesis of asthma attacks in rhinovirus (RV) infections. However, the association between increased RV replication and enhanced expression of intercellular adhesion molecule‐1 (ICAM‐1), a receptor for a major RV group, in airway epithelial cells has remained unclear. Furthermore, the inhibitory effects of mucolytics, which have clinical benefits in asthmatic subjects, are uncertain. Human nasal epithelial (HNE) cells were infected with type 14 rhinovirus (RV14), a major RV group. RV14 titers and cytokine concentrations, including interleukin (IL)‐6 and IL‐8, in supernatants, RV14 RNA replication and susceptibility to RV14 infection were higher in HNE cells obtained from subjects in the allergic group (allergic subjects) than in those from subjects in the non‐allergic group (non‐allergic subjects). ICAM‐1 expression and the number and fluorescence intensity of acidic endosomes from which RV14 RNA enters the cytoplasm were higher in HNE cells from allergic subjects, though substantial amounts of interferon (IFN)‐γ and IFN‐λ were not detected in the supernatant. The abundance of p50 and p65 subunits of transcription factor nuclear factor kappa B (NF‐κB) in nuclear extracts of the cells from allergic subjects was higher compared to non‐allergic subjects, and an inhibitor of NF‐κB, caffeic acid phenethyl ester, reduced the fluorescence intensity of acidic endosomes as well as RV titers and RNA. Furthermore, a mucolytic agent, L‐carbocisteine, reduced RV14 titers and RNA levels, cytokine release, ICAM‐1 expression, the fluorescence intensity of acidic endosomes, and NF‐κB activation. The increased RV14 replication observed in HNE cells from allergic subjects might be partly associated with enhanced ICAM‐1 expression and decreased endosomal pH through NF‐κB activation. L‐Carbocisteine inhibits RV14 infection by reducing ICAM‐1 and acidic endosomes and may, therefore, modulate airway inflammation caused by RV infection in allergic subjects.

Interferon response of the cystic fibrosis bronchial epithelium to major and minor group rhinovirus infection

Rhinoviruses (RVs) are associated with exacerbations of cystic fibrosis (CF), asthma and COPD. There is growing evidence suggesting the involvement of the interferon (IFN) pathway in RV-associated morbidity in asthma and COPD. The mechanisms of RV-triggered exacerbations in CF are poorly understood. In a pilot study, we assessed the antiviral response of CF and healthy bronchial epithelial cells (BECs) to RV infection, we measured the levels of IFNs, pattern recognition receptors (PRRs) and IFN-stimulated genes (ISGs) upon infection with major and minor group RVs and poly(IC) stimulation. Major group RV infection of CF BECs resulted in a trend towards a diminished IFN response at the level of IFNs, PRRs and ISGs in comparison to healthy BECs. Contrary to major group RV, the IFN pathway induction upon minor group RV infection was significantly increased at the level of IFNs and PRRs in CF BECs compared to healthy BECs.

Developing Strategies to Treat Asthma Exacerbations Caused by Rhinovirus

Developing Strategies to Treat Asthma Exacerbations Caused by Rhinovirus

Mouse models of rhinovirus infection and airways disease.

Mouse models are invaluable tools for gaining insight into host immunity during virus infection. Until recently, no practical mouse model for rhinovirus infection was available. Development of infection models was complicated by the existence of distinct groups of viruses that utilize different host cell surface proteins for binding and entry. Here, we describe mouse infection models, including virus purification and measurement of host immune responses, for representative viruses from two of these groups: (1) infection of unmodified Balb/c mice with minor group rhinovirus serotype 1B (RV-1B) and (2) infection of transgenic Balb/c mice with major group rhinovirus serotype 16 (RV-16).

The cellular receptor for enterovirus 71.

The cellular receptor for enterovirus 71.