Human Rhinovirus Infection Research Articles

Epidemiological analysis and follow-up of human rhinovirus infection in children with asthma exacerbation.

To determine the prevalence of human rhinovirus (HRV) infection in children with acute asthma exacerbations, investigation of HRV viral load and severity of asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were collected and assessed for respiratory viruses. HRV‐positive samples were sequenced to identify types and determine viral load. Outpatients with asthma exacerbations underwent follow‐up evaluations, their swabs were collected and clinical outcomes were recorded at their next clinic visit 4 weeks later. One hundred forty‐three inpatients and 131 outpatients, including 88 patients with asthma exacerbations and 43 controls with stable asthma were recruited. HRV‐A was mainly detected in September and February (45.5% and 33.3%, respectively), while HRV‐C was mainly detected in November and April (70.0% and 55.6%, respectively). HRV‐C was the primary type and was primarily found in inpatients with severe asthma exacerbations. HRV‐A viral load in the group of inpatients with severe exacerbations was higher than in the mild and moderate groups (P < 0.001 and P = 0.022). The HRV‐A viral load of both inpatients and outpatients was higher than that of HRV‐C (P < 0.001 and P = 0.036). The main genotypes were HRV‐C53 and HRV‐A20 among inpatients, and this genotype caused more severe clinical manifestations. HRV persisted for no more than 4 weeks, and their symptoms or signs of disease were well‐controlled well. HRV‐C was most frequently detected in asthma exacerbations. HRV‐A with high viral load led to severe asthma exacerbations.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents

ABSTRACTObjective: It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. Methods: Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. Results: HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2–13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8–47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9–11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2–6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). Conclusion: Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

Detection and genotyping of rhinovirus from exacerbated asthmatic patients in Baghdad, Iraq

Asthma is a chronic disease with multiple environmental and genetic causes. Determining the role of rhinovirus in asthma incidence and exacerbation could improve the controlling measures for this disease. This study aims to detect and genotype human rhinovirus (HRV) in asthmatic patients in Iraqi population. A total of 45 patients with asthma participated in this study. Viral RNA was extracted from nasopharyngeal swabs (NPS) and cDNA was created using reverse transcriptase-polymerase chain reaction (PCR). Specific primers for HRV were used with two rounds nested-PCR to amplify the 5’-noncoding region of the viral genome. PCR products of the second round nested-PCR underwent direct sequencing and the resultant sequences were aligned with reference sequences in GenBank. MEGA 5 software was used to construct phylogenetic tree between eight successfully sequenced isolates and eight reference isolates. Alignment of viral sequence revealed highly genetic diversity between these sequences and the reference isolates. Phylogenetic tree showed that five isolates belong to Human Rhinovirus- A (HRV-A), while three isolate belong to Human Rhinovirus-C (HRV-C). The HRV-C was detected and genotyped for the first time in Iraq. The results of the current study suggest the significant role of HRV infection among patients with exacerbated asthma in Iraq. Key words: Human rhinovirus, genotyping, asthma exacerbation.

Phenotypical characterization of human rhinovirus infections in severely premature children

BackgroundHuman Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV.MethodsWe conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve (hypoxemia and tachypnea) in young children with HRV infections. Demographic and clinical variables were obtained from reviewing electronic medical records (EMR).ResultsThis study included a total of 205 children; 71% of these children were born full-term (>37 weeks gestation), 10% preterm (32–37 weeks) and 19% severely premature (<32 weeks). Our results demonstrated that: 1) HRV infections in the first 3 years of life were associated with higher overall respiratory distress scores in severely premature children relative to children born preterm or full-term; 2) HRV-infected severely premature children ≤3 years old were more likely to have lower airway obstruction than HRV-infected children born preterm or full-term; and 3) other clinical signs of respiratory distress such as tachypnea and hypoxemia were not more common in severely premature than in preterm and full-term children during an HRV infection.ConclusionsOur results indicate that HRV infections in severely premature children are associated with lower airway obstruction rather than hypoxemia or tachypnea. The latter suggests that enhanced airway reactivity is the underlying mechanism for the increased susceptibility to HRV in severely premature children. Longitudinal studies are needed to understand why premature babies develop airway hyper-reactivity to HRV and the long-term effects of early HRV infection in this population.

Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection.

Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine.

Comparison of clinical features between respiratory syncytial virus and human rhinovirus lower respiratory tract infection in infants between 2013-2015 in Suzhou

Objective To analyze the clinical features of infants infected by respiratory syncytial virus (RSV) or human rhinovirus (HRV) in lower respiratory tract in Suzhou area based on the month age and the month of the year. Methods From January 2013 to December 2015, 2 206 nasopharyngeal aspirates specimens were collected from the infants with lower respiratory tract infection. Direct immunofluorescence assay was performed to test RSV.Reverse transcription-polymerase chain reaction(RT-PCR) method was used to test HRV.The medical history was collected and pulmonary function tests were performed in some infants who were infected with RSV and HRV. Results In 2 206 cases, total RSV positive rate was 19.90%(439/2 206 cases) and simple RSV infection positive was detected in 399 cases. Total HRV positive rate was 14.14%(312/2 206 cases), in which simple HRV infection positive was detected in 250 cases and the detection rate of RSV was significantly higher than that of HRV(χ2=25.88, P 1-2 month, >2-3 month and >3-4 months respectively.Up to the age of 4 months old, the detection rate decreased gradually, and with the increase of age and the detection rate in >7-8 month group was only 10.96%(16/146 cases). The detection rate of HRV was 0(0/12)and 9.40%(44/468 cases) in the age group of 28 d-1 month, >1-2 month, respectively. After 2 months age old, the detection rate fluctuation ranged from 13.22% to 16.67%.The incidence rate of severe RSV infection was 12.30%(54/439 cases) and the incidence rate of severe HRV infection was 5.13%(16/312 cases). Increased respiratory rate was more common in patients with severe RSV infection while severe HRV infection in infants were accompanied by multiple lobar involvement.After RSV infection, the incidence rate of pulmonary function damage was 89.03%(276/310 cases). After HRV infection, 89.27%(183/205 cases)of the infants suffered from pulmonary function damage. Both RSV and HRV infection might cause pulmonary function damage. Conclusions RSV and HRV are the major pathogens in infants of Suzhou areas. The incidence of RSV-induced wheezing is significantly higher than that of HRV. RSV is detected positive mainly in winter and early spring and the infants within 4-month old are susceptible population.HRV is detected positive mainly in June, July and September and the infants older than 2 months are susceptible population. The incidence of severe RSV infection is significantly higher than that of HRV. Severe RSV infection may cause increased respiratory rate and severe HRV infection mainly cause multiple lobar involvement. RSV and HRV infection may cause pulmonary function damage. Key words: Infants; Respiratory syncytial virus; Human rhinovirus

Cathelicidins display conserved direct antiviral activity towards rhinovirus

Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract infections, and are associated with significant morbidity and mortality in immunocompromised individuals and patients with pre-existing pulmonary conditions. The therapeutic options available are extremely limited and therefore novel therapeutics for HRV infections are of significant interest. Cathelicidins have been shown to have potent antiviral activity against a range of pathogens and are known to be key immunomodulatory mediators during infection. We therefore assessed the antiviral potential of cathelicidins from humans and other mammalian species against HRV, together with the potential for the human cathelicidin to modulate apoptotic pathways and alter cell viability during HRV infection. We demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this activity is visible when either the virus is exposed to the peptides prior to cell infection or after cells have been infected. We further demonstrate that, in contrast to established findings with bacterial infection models, LL-37 does not induce apoptosis or necrosis in HRV-infected lung epithelial cells at physiological or superphysiological concentrations, but does reduce the metabolic activity of infected cells compared to uninfected cells treated with similar peptide concentrations. Collectively, the findings from this study demonstrate that the mechanism of action of cathelicidins against rhinovirus is by directly affecting the virus and we propose that the delivery of exogenous cathelicidins, or novel synthetic analogues, represent an exciting and novel therapeutic strategy for rhinovirus infection.

Design, synthesis and evaluation of 2,2-dimethyl-1,3-dioxolane derivatives as human rhinovirus 3C protease inhibitors

The human rhinovirus (HRV) is the most significant cause of the common cold all over the world. The maturation and replication of this virus entirely depend on the activity of a virus-encoded 3C protease. Due to the high conservation among different serotypes and the minimal homology existing between 3C protease and known mammalian enzymes, 3C protease has been regarded as an attractive target for the treatment of HRV infections. In this study, we identified a novel (4R,5R)-N4-(2-((3-methoxyphenyl)amino)ethyl)-2,2-dimethyl-N5-(naphthalen-2-yl)-1,3-dioxolane-4,5-dicarboxamide (7a) to be a HRV 3C protease inhibitor via virtual screening. Further research has been focused on the design, synthesis and in vitro biological evaluation of 7a derivatives. The studies revealed that compound 7d has an IC50 value of 2.50±0.7µM against HRV 3C protease, and it thus could serve as a promising compound for the development of novel anti-rhinoviral medicines.

Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo

Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2′,2′-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model. Intranasal administration of gemcitabine significantly lowered pulmonary viral load and inflammation by decreasing proinflammatory cytokines, including TNF-α and IL-1β, and reduction in the number of lung-infiltrating lymphocytes. Interestingly, we found that the addition of UTP and CTP significantly attenuated the antiviral activity of gemcitabine. Thus the limitation of UTP and CTP by the addition of gemcitabine may inhibit the viral RNA synthesis. These results suggest that gemcitabine, an antineoplastic drug, can be repositioned as an antiviral drug to inhibit HRV infection.

Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration.

Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell (ASMC) mass with a greater proximity of the ASMCs to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMCs. ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer (ACEA Biosciences Inc., San Diego, CA). Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8, and CXCL10 were also examined. Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMCs with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were the most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8, and CXCL10 were used at levels found in epithelial supernatants, they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration, and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis and thus may contribute to the pathogenesis of airway remodeling in patients with asthma.

Role of human rhinovirus in triggering human airway epithelial-mesenchymal transition

BackgroundStructural changes in the airways, collectively referred to as airway remodeling, are a characteristic feature of asthma, and are now known to begin in early life. Human rhinovirus (HRV)-induced wheezing illnesses during early life are a potential inciting stimulus for remodeling. Increased deposition of matrix proteins causes thickening of the lamina reticularis, which is a well-recognized component of airway remodeling. Increased matrix protein deposition is believed to be due to the presence of increased numbers of activated mesenchymal cells (fibroblasts/myofibroblasts) in the subepithelial region of asthmatic airways. The origin of these increased mesenchymal cells is not clear, but one potential contributor is the process of epithelial-mesenchymal transition (EMT). We hypothesized that HRV infection may help to induce EMT.MethodsWe used the BEAS-2B human bronchial epithelial cells line, which uniformly expresses the major group HRV receptor, to examine the effects of stimulation with HRV alone, transforming growth factor-β1 (TGF-β1), alone, and the combination, on induction of changes consistent with EMT. Western blotting was used to examine expression of epithelial and mesenchymal phenotypic marker proteins and selected signaling molecules. Cell morphology was also examined.ResultsIn this study, we show that two different strains of HRV, which use two different cellular receptors, are each capable of triggering phenotypic changes consistent with EMT. Moreover, both HRV serotypes synergistically induced changes consistent with EMT when used in the presence of TGF-β1. Morphological changes were also most pronounced with the combination of HRV and TGF-β1. Viral replication was not essential for phenotypic changes. The synergistic interactions between HRV and TGF-β1 were mediated, at least in part, via activation of mitogen activated protein kinase pathways, and via induction of the transcription factor SLUG.ConclusionsThese data support a role for HRV in the induction of EMT, which may contribute to matrix protein deposition and thickening of the lamina reticularis in airways of patients with asthma.

Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells.

Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.

Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years

ObjectivesTo report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. MethodsThis was a cross‐sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. ResultsHRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co‐detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV‐infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p=0.006), but had more comorbidities (40% and 27%, respectively; p=0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r=−0.636, p<0.001) but no correlation with rainfall (r=−0.036, p=0.866). ConclusionHRV is usually detected in hospitalized children with respiratory infections and is often present in viral co‐detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons.

Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes.

Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation.

Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication.

ABSTRACTPicornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi membrane vesicular and lipid transport, we hypothesized that PKD played a role in viral replication. We present multiple lines of evidence in support of this hypothesis. First, infection of HeLa cells with human rhinovirus (HRV) induced the phosphorylation of PKD. Second, PKD inhibitors reduced HRV genome replication, protein expression, and titers in a concentration-dependent fashion and also blocked the replication of poliovirus (PV) and foot-and-mouth disease virus (FMDV) in a variety of cells. Third, HRV replication was significantly reduced in HeLa cells overexpressing wild-type and mutant forms of PKD1. Fourth, HRV genome replication was reduced in HAP1 cells in which the PKD1 gene was knocked out by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Although we have not identified the molecular mechanism through which PKD regulates viral replication, our data suggest that this is not due to enhanced interferon signaling or an inhibition of clathrin-mediated endocytosis, and PKD inhibitors do not need to be present during viral uptake. Our data show for the first time that targeting PKD with small molecules can inhibit the replication of HRV, PV, and FMDV, and therefore, PKD may represent a novel antiviral target for drug discovery.IMPORTANCE Picornaviruses remain an important family of human and animal pathogens for which we have a very limited arsenal of antiviral agents. HRV is the causative agent of the common cold, which in itself is a relatively trivial infection; however, in asthma and chronic obstructive pulmonary disease (COPD) patients, this virus is a major cause of exacerbations resulting in an increased use of medication, worsening symptoms, and, frequently, hospital admission. Thus, HRV represents a substantial health care and economic burden for which there are no approved therapies. We sought to identify a novel host target as a potential anti-HRV therapy. HRV infection induces the phosphorylation of PKD, and inhibitors of this kinase effectively block HRV replication at an early stage of the viral life cycle. Moreover, PKD inhibitors also block PV and FMDV replication. This is the first description that PKD may represent a target for antiviral drug discovery.

Interference Between Respiratory Syncytial Virus and Human Rhinovirus Infection in Infancy.

Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines. To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Children's Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses. Among 3263 respiratory tract samples, 24.5% (798) and 37.3% (1216) were RSV and HRV positive, respectively. The odds of HRV infection were significantly lower in RSV-infected infants in all cohorts, with adjusted odds ratios of 0.30 (95% confidence interval [CI], .22-.40 in the INSPIRE study, 0.18 (95% CI, .11-.28) in the TCRI (adjusted for disease severity), and 0.34 (95% CI, .16-.72) in the MAKI trial. HRV infection was significantly more common among infants administered RSV immunoprophylaxis, compared with infants who did not receive immunoprophylaxis (OR, 1.65; 95% CI, 1.65-2.39). A negative association of RSV on HRV codetection was consistently observed across populations, seasons, disease severity, and geographical regions. Suppressing RSV infection by RSV immunoprophylaxis might increase the risk of having HRV infection.

Clinical and epidemiological profiles including meteorological factors of low respiratory tract infection due to human rhinovirus in hospitalized children

BackgroundLower respiratory tract infection (LRTI) is a major cause of morbidity and mortality in children. Human rhinovirus (HRV) is confirmed to be associated with pediatric lower respiratory tract infection. Seasonal and meteorological factors may play a key role in the epidemiology of HRV. The purposes of this study were to investigate the frequency, seasonal distribution, and clinical characteristics of hospitalized children with LRTI caused by HRVs. In addition, associations between incidence of HRVs and meteorological factors in a subtropical region of China were discussed.MethodsHospitalized children <14 years old admitted to the Respiratory Department of the Children’s Hospital, which is affiliated to Soochow University, between January 1, 2013 and December 31, 2015, were enrolled in this study. Multi-pathogens were detected in nasopharyngeal aspirate samples. Meanwhile, meteorological factors were recorded.ResultsThe average incidence of HRVs infection was 11.4% (707/6194) and 240 cases of which were co-infection cases with other pathogens. Children with co-infection presented more frequent fever and tachypnea compared to children infected with HRVs only (both P < 0.05). Among 707 HRV positive children, the mean age was 23.2 months (range 1 to 140 months). Among all respiratory infections, the highest incidence of HRVs cases occurred in children age 13–36 months old (15.1%, 203/1341). Of all 228 HRV cases in 2014, 85 cases (37.3%) were HRV-C positive. HRVs and HRV-C infection occurred throughout the year during the study period, although a higher incidence was observed in summer and autumn seasons. HRVs or HRV-C incidence in hospitalized children with LRTI was associated with the monthly mean temperature (both P < 0.05).ConclusionHRV was one of the most common viral pathogen detected in hospitalized children with LRTI at the Children’s Hospital of Suzhou, China, and had its own seasonal distribution including HRV-C, which was partly caused by temperature.

15 - Human Rhinovirus Infections in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Tract Disease

15 - Human Rhinovirus Infections in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Tract Disease

In Vivo Persistence of Human Rhinoviruses in Immunosuppressed Patients.

Several species of the genus Enterovirus cause persistent infections in humans. Human rhinovirus (HRV) infections are generally self-limiting but occasionally persistent infections have been described. This study aimed to identify persistent HRV infections and investigate the clinical and virologic characteristics of patients with persistent infections. From January 2012 to March 2015, 3714 respiratory specimens from 2608 patients were tested for respiratory viruses by using a multiplex reverse transcription–polymerase chain reaction. A retrospective study was performed. Patients with at least two specimens positive for HRV/enterovirus taken 45 days or longer apart were identified and the HRV/enteroviruses were typed. Patients with persistent infection were compared to patients with reinfection and patients with cleared infection. Phylogenetic analysis of the viral protein(VP)4/VP2 region was performed. 18 patients with persistent HRV/enterovirus infection were identified. Minimum median duration of persistence was 92 days (range 50–455 days). All but one patients with persistence were immunosuppressed. Immunosuppression and hematologic disorders were more frequent in patients with persistence (n = 18) than in patients with reinfection (n = 33) and with cleared infection (n = 25) (p = 0.003 and p = 0.001, respectively). In conclusion, this retrospective study identified HRV persistence in vivo which occurred mainly in immunosuppressed patients.

Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations

SummaryBackgroundHuman rhinoviruses (HRVs) are a major trigger of asthma exacerbations, with the bronchial epithelium being the major site of HRV infection and replication. Mast cells (MCs) play a key role in asthma where their numbers are increased in the bronchial epithelium with increasing disease severity.ObjectiveIn view of the emerging role of MCs in innate immunity and increased localization to the asthmatic bronchial epithelium, we investigated whether HRV infection of MCs generated innate immune responses which were protective against infection.MethodsThe LAD2 MC line or primary human cord blood‐derived MCs (CBMCs) were infected with HRV or UV‐irradiated HRV at increasing multiplicities of infection (MOI) without or with IFN‐β or IFN‐λ. After 24 h, innate immune responses were assessed by RT‐qPCR and IFN protein release by ELISA. Viral replication was determined by RT‐qPCR and virion release by TCID 50 assay.Results HRV infection of LAD2 MCs induced expression of IFN‐β, IFN‐λ and IFN‐stimulated genes. However, LAD2 MCs were permissive for HRV replication and release of infectious HRV particles. Similar findings were observed with CBMCs. Neutralization of the type I IFN receptor had minimal effects on viral shedding, suggesting that endogenous type I IFN signalling offered limited protection against HRV. However, augmentation of these responses by exogenous IFN‐β, but not IFN‐λ, protected MCs against HRV infection.Conclusion and Clinical Relevance MCs are permissive for the replication and release of HRV, which is prevented by exogenous IFN‐β treatment. Taken together, these findings suggest a novel mechanism whereby MCs may contribute to HRV‐induced asthma exacerbations.