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Infectious Disease Clinics of North... Mar 2018Respiratory viral infections are a leading cause of pediatric disease. Emerging respiratory viruses can cause outbreaks with significant morbidity and mortality or... (Review)
Review
Respiratory viral infections are a leading cause of pediatric disease. Emerging respiratory viruses can cause outbreaks with significant morbidity and mortality or circulate routinely. The rapid identification of pathogens, epidemiologic tracing, description of symptoms, and development of preventative and therapeutic measures are crucial to limiting the spread of these viruses. Some emerging viruses, such as rhinovirus C and influenza C, circulate yearly but were previously undetected due to limited diagnostic methods. Although some pathogens have a geographic focus, globalization dictates that providers be aware of all emerging diseases in order to recognize outbreaks and diagnose and treat patients.
Topics: Child; Child, Preschool; Communicable Diseases, Emerging; Coronavirus Infections; Disease Outbreaks; Humans; Influenza, Human; Molecular Diagnostic Techniques; Mutation; Orthomyxoviridae; Reassortant Viruses; Virus Diseases; Viruses
PubMed: 29406977
DOI: 10.1016/j.idc.2017.10.001 -
American Journal of Respiratory and... Apr 2021Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. To identify how age and other... (Comparative Study)
Comparative Study
Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits ( < 0.001, χ) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5-27%) at the age of 2 years, but by the age of 16 years, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A; < 0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age ( < 0.0001), genotype ( < 0.05), and wheezing illnesses ( < 0.05). Furthermore, certain RV types (e.g., C2, C11, A78, and A12) were consistently more virulent and prevalent over time. Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.
Topics: Adolescent; Age Factors; Antibodies, Neutralizing; Asthma; Australia; Child; Child, Preschool; Cohort Studies; Disease Susceptibility; Female; Finland; Genetic Variation; Genotype; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Picornaviridae Infections; Respiratory Sounds; Rhinovirus; United States
PubMed: 33357024
DOI: 10.1164/rccm.202010-3753OC -
The Pediatric Infectious Disease Journal Apr 2020Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations... (Observational Study)
Observational Study
BACKGROUND
Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity.
METHODS
This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3-23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008.
RESULTS
Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing.
CONCLUSIONS
Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.
Topics: Child, Preschool; Enterovirus; Female; Fever; Finland; Humans; Infant; Male; Picornaviridae Infections; Prospective Studies; Respiratory Sounds; Respiratory Tract Infections; Retrospective Studies; Rhinovirus
PubMed: 31876616
DOI: 10.1097/INF.0000000000002570 -
Microbes and Infection Jun 2012A newly discovered group of human rhinoviruses (HRVs) has been classified as the HRV-C species based on distinct genomic features. HRV-Cs circulate worldwide, and are... (Review)
Review
A newly discovered group of human rhinoviruses (HRVs) has been classified as the HRV-C species based on distinct genomic features. HRV-Cs circulate worldwide, and are important causes of upper and lower respiratory illnesses. Methods to culture and produce these viruses have recently been developed, and should enable identification of unique features of HRV-C replication and biology.
Topics: Base Sequence; Common Cold; Genetic Variation; Humans; Molecular Sequence Data; Picornaviridae Infections; Recombination, Genetic; Rhinovirus; Virus Cultivation
PubMed: 22285901
DOI: 10.1016/j.micinf.2011.12.011 -
Frontiers in Immunology 2021Rhinovirus C (RV-C) infection is associated with severe asthma exacerbations. Since type 2 inflammation is an important disease mechanism in asthma, we hypothesized that...
Rhinovirus C (RV-C) infection is associated with severe asthma exacerbations. Since type 2 inflammation is an important disease mechanism in asthma, we hypothesized that RV-C infection, in contrast to RV-A, preferentially stimulates type 2 inflammation, leading to exacerbated eosinophilic inflammation. To test this, we developed a mouse model of RV-C15 airways disease. RV-C15 was generated from the full-length cDNA clone and grown in HeLa-E8 cells expressing human CDHR3. BALB/c mice were inoculated intranasally with 5 x 10 ePFU RV-C15, RV-A1B or sham. Mice inoculated with RV-C15 showed lung viral titers of 1 x 10 TCID units 24 h after infection, with levels declining thereafter. IFN-α, β, γ and λ2 mRNAs peaked 24-72 hrs post-infection. Immunofluorescence verified colocalization of RV-C15, CDHR3 and acetyl-α-tubulin in mouse ciliated airway epithelial cells. Compared to RV-A1B, mice infected with RV-C15 demonstrated higher bronchoalveolar eosinophils, mRNA expression of IL-5, IL-13, IL-25, Muc5ac and Gob5/Clca, protein production of IL-5, IL-13, IL-25, IL-33 and TSLP, and expansion of type 2 innate lymphoid cells. Analogous results were found in mice treated with house dust mite before infection, including increased airway responsiveness. In contrast to littermates, RV-C-infected mice deficient in ILC2s failed to show eosinophilic inflammation or mRNA expression of IL-13, Muc5ac and Muc5b. We conclude that, compared to RV-A1B, RV-C15 infection induces ILC2-dependent type 2 airway inflammation, providing insight into the mechanism of RV-C-induced asthma exacerbations.
Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cadherin Related Proteins; Cadherins; Coxsackievirus Infections; Disease Models, Animal; Enterovirus; Eosinophilia; Eosinophils; Female; HeLa Cells; Humans; Immunity, Innate; Lymphocytes; Membrane Proteins; Mice; Mice, Transgenic; Nuclear Receptor Subfamily 1, Group F, Member 1; Symptom Flare Up
PubMed: 33968043
DOI: 10.3389/fimmu.2021.649520 -
PLoS Pathogens Jan 2022The clinical impact of rhinovirus C (RV-C) is well-documented; yet, the viral life cycle remains poorly defined. Thus, we characterized RV-C15 replication at the...
The clinical impact of rhinovirus C (RV-C) is well-documented; yet, the viral life cycle remains poorly defined. Thus, we characterized RV-C15 replication at the single-cell level and its impact on the human airway epithelium (HAE) using a physiologically-relevant in vitro model. RV-C15 replication was restricted to ciliated cells where viral RNA levels peaked at 12 hours post-infection (hpi), correlating with elevated titers in the apical compartment at 24hpi. Notably, infection was associated with a loss of polarized expression of the RV-C receptor, cadherin-related family member 3. Visualization of double-stranded RNA (dsRNA) during RV-C15 replication revealed two distinct replication complex arrangements within the cell, likely corresponding to different time points in infection. To further define RV-C15 replication sites, we analyzed the expression and colocalization of giantin, phosphatidylinositol-4-phosphate, and calnexin with dsRNA. Despite observing Golgi fragmentation by immunofluorescence during RV-C15 infection as previously reported for other RVs, a high ratio of calnexin-dsRNA colocalization implicated the endoplasmic reticulum as the primary site for RV-C15 replication in HAE. RV-C15 infection was also associated with elevated stimulator of interferon genes (STING) expression and the induction of incomplete autophagy, a mechanism used by other RVs to facilitate non-lytic release of progeny virions. Notably, genetic depletion of STING in HAE attenuated RV-C15 and -A16 (but not -B14) replication, corroborating a previously proposed proviral role for STING in some RV infections. Finally, RV-C15 infection resulted in a temporary loss in epithelial barrier integrity and the translocation of tight junction proteins while a reduction in mucociliary clearance indicated cytopathic effects on epithelial function. Together, our findings identify both shared and unique features of RV-C replication compared to related rhinoviruses and define the impact of RV-C on both epithelial cell organization and tissue functionality-aspects of infection that may contribute to pathogenesis in vivo.
Topics: Cells, Cultured; Cytopathogenic Effect, Viral; Endoplasmic Reticulum; Enterovirus; Humans; Respiratory Mucosa; Virus Replication
PubMed: 34995322
DOI: 10.1371/journal.ppat.1010159 -
Clinical and Translational Allergy 2019Rhinovirus A and C infections are important contributors to asthma induction and exacerbations. No data exist on the interaction of local immune responses in rhinovirus...
BACKGROUND
Rhinovirus A and C infections are important contributors to asthma induction and exacerbations. No data exist on the interaction of local immune responses in rhinovirus infection. Therefore, we aimed to determine the tonsillar immune responses according to rhinovirus A, B and C infections.
METHODS
We collected tonsillar samples, nasopharyngeal aspirates and peripheral blood from 42 rhinovirus positive tonsillectomy patients. Fifteen respiratory viruses or their types were investigated from nasopharynx and tonsil tissue, and rhinovirus species were typed. The expression of 10 cytokines and 4 transcription factors (IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet) were studied from tonsil tissue by quantitative PCR. A standard questionnaire of respiratory symptoms and health was filled by the patient or his/her guardian. The patients were divided into three groups by the determination of rhinovirus species.
RESULTS
Overall, 16 patients had rhinovirus A, 12 rhinovirus B and 14 rhinovirus C infection. In rhinovirus B positive group there were significantly less men ( = 0.0072), less operated in spring ( = 0.0096) and more operated in fall ( = 0.030) than in rhinovirus A or C groups. Rhinovirus A positive patients had more respiratory symptoms ( = 0.0074) and particularly rhinitis ( = 0.036) on the operation day. There were no significant differences between the groups in virus codetection. In adjusted analysis, rhinovirus C infections were associated with increased IFN-α ( = 0.045) and decreased RORC2 expression ( = 0.025).
CONCLUSIONS
Rhinovirus species associated differently with clinical characteristics and tonsillar cytokine responses.
PubMed: 31827765
DOI: 10.1186/s13601-019-0302-7 -
American Journal of Respiratory and... Apr 2021
Topics: Antibodies, Neutralizing; Enterovirus; Enterovirus Infections; Humans; Rhinovirus; Vaccines
PubMed: 33600736
DOI: 10.1164/rccm.202102-0346ED -
Viruses Jul 2023Rhinoviruses (RV) are one of the most common causative agents of respiratory infections, with significant socioeconomic impact. RV infections are not notifiable in...
Rhinoviruses (RV) are one of the most common causative agents of respiratory infections, with significant socioeconomic impact. RV infections are not notifiable in Bulgaria, and little is known about the different RV genotypes circulating in the country. This study aims to investigate the diversity of RV genotypes that were circulating in Bulgaria in the period 2018-2021 in samples from ILI/ARI patients. Genotype assignment was based on sequencing and phylogenetic analysis of the 5' untranslated region and the VP4-VP2 region. Out of a total of 1385 nasopharyngeal swabs tested, 166 were RV-positive (RV detection rate: 11.99% (166/1385)). Those with a cycle threshold <25 were selected for genotyping (n = 63). RV isolates were successfully genotyped and classified into 34 genotypes within (RV-A) (RV-B) and (RV-C) species. Presumptive recombination events between the 5'UTR and VP4-VP2 regions were detected in three of the isolates. RV-A and RV-C were the prevalent RV species, with significantly more frequent detections of RV-A in the years before the COVID-19 pandemic compared to the post-pandemic period, when RV-C prevailed. The present study is the first to determine RV genotypes in Bulgaria and the circulation of RV-C has been described for the first time in the country.
Topics: Humans; Rhinovirus; Phylogeny; Bulgaria; Pandemics; Picornaviridae Infections; COVID-19; Genotype; Enterovirus Infections; Respiratory Tract Infections; 5' Untranslated Regions
PubMed: 37515294
DOI: 10.3390/v15071608 -
Journal of Microbiology, Immunology,... Aug 2020Human rhinovirus type C (HRV-C) has been associated with asthma exacerbation (AE) in children in several countries. However, in Taiwan the association between HRV,...
BACKGROUND/PURPOSES
Human rhinovirus type C (HRV-C) has been associated with asthma exacerbation (AE) in children in several countries. However, in Taiwan the association between HRV, especially HRV-C, and AE in children has yet to be elucidated. We sought to investigate the prevalence of respiratory viruses in children with acute lower respiratory tract infection (ALRTI) in Taiwan and the association between different types of HRV and AE in children.
METHODS
This prospective study was conducted from 2011 to 2013, and enrolled children with ALRTI, including an asthma exacerbation group (AE; n = 28) and a Non-asthma group (n = 66). Viruses were detected by culture, reverse transcription-polymerase chain reaction, and molecular sequencing of nasopharyngeal swabs.
RESULTS
The prevalence of identified respiratory viruses was 78.6% in the AE group and 65.2% in the Non-asthma group. The prevalence rates of HRV and HRV-C were significantly higher in the AE group than in the Non-asthma group (67.9% vs. 33.3% in HRV, p = 0.002; and 50% vs. 15.2% in HRV-C, p < 0.001). Among the children with HRV, the prevalence of HRV-C (68.4%) was higher than that of the other types of HRV (31.6%, including HRV-A 26.3%, and HRV-B 5.3%) in the AE group but not in the Non-asthma group (40.9% vs. 59.1%).
CONCLUSIONS
HRV is the most predominant viral infection responsible for pediatric AE in Taiwan, and HRV-C is responsible for more of these exacerbations than HRV-A or HRV-B.
Topics: Asthma; Child; Child, Preschool; Enterovirus; Female; Humans; Infant; Infant, Newborn; Male; Nasopharynx; Picornaviridae Infections; Prevalence; Prospective Studies; Respiratory Tract Infections; Seasons; Symptom Flare Up; Taiwan
PubMed: 30591259
DOI: 10.1016/j.jmii.2018.12.001