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The Journal of Allergy and Clinical... Mar 2022Rhinovirus infections can cause wheezing illnesses in all age groups. In preschool children, rhinovirus infections frequently initiate acute wheezing illnesses. Children... (Review)
Review
Rhinovirus infections can cause wheezing illnesses in all age groups. In preschool children, rhinovirus infections frequently initiate acute wheezing illnesses. Children who wheeze with rhinoviruses are at increased risk to go on to develop asthma. Once asthma is established, rhinovirus infections are potent triggers for acute airway obstruction and exacerbations in children and adults. Paradoxically, for most individuals, rhinovirus infections commonly cause cold symptoms with little or no involvement of the lower airways. This paradox has led investigators to identify specific risk factors and mechanisms for rhinovirus wheezing, and this review will outline progress in 3 main areas. First, the 3 species of rhinoviruses have different patterns of infection and virulence. Second, personal factors such as lung function and immunity influence lower respiratory outcomes of rhinovirus infection. The mucosal immune response is critical, and the quality of the interferon response and allergic inflammation interacts to determine the risk for rhinovirus wheezing. Finally, rhinovirus infections can promote pathogen-dominated airway microbiota that increase the risk for wheezing. Although specific antivirals for rhinovirus are still not available, identifying risk factors for wheezing illnesses has provided several other potential targets and strategies for reducing the risk of rhinovirus-induced wheezing and exacerbations of asthma.
Topics: Adult; Antiviral Agents; Asthma; Child, Preschool; Communicable Diseases; Humans; Microbiota; Picornaviridae Infections; Respiratory Sounds; Rhinovirus
PubMed: 35074599
DOI: 10.1016/j.jaip.2022.01.006 -
Viruses Jun 2019Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one... (Review)
Review
Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection's epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.
Topics: Adaptive Immunity; Antiviral Agents; Asthma; Bronchiolitis; Child; Child Health; Humans; Immunity, Cellular; Infant; Inflammation; Picornaviridae Infections; Respiratory Hypersensitivity; Respiratory Sounds; Rhinovirus; Serogroup; Viral Vaccines
PubMed: 31195744
DOI: 10.3390/v11060521 -
Nature Communications Apr 2023Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the...
Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.
Topics: Humans; Antiviral Restriction Factors; Asthma; COVID-19; DEAD Box Protein 58; Enterovirus Infections; Inflammasomes; Inflammation; Interferon Type I; Picornaviridae Infections; Rhinovirus; SARS-CoV-2
PubMed: 37087523
DOI: 10.1038/s41467-023-37470-4 -
The Journal of Allergy and Clinical... Oct 2017Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis,... (Review)
Review
Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.
Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchiolitis; Child; Disease Progression; Humans; Microbiota; Palivizumab; Respiratory Sounds; Respiratory Syncytial Viruses; Rhinovirus; Risk; Virulence; Virus Diseases
PubMed: 28987219
DOI: 10.1016/j.jaci.2017.08.003 -
Virology Journal Oct 2018Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in...
BACKGROUND
Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in the hospitalized patients. Sensitive and accurate detection of RSV, HRV and HMPV is necessary for clinical diagnosis and treatment.
RESULTS
A locked nucleic acid (LNA)-based multiplex closed one-tube nested real-time RT-PCR (mOTNRT-PCR) assay was developed for simultaneous detection of RSV, HRV and HMPV. The sensitivity, specificity, reproducibility and clinical performance of mOTNRT-PCR were evaluated and compared with individual real time PCR (RT-qPCR) assay using clinical samples. The analytical sensitivity of mOTNRT-PCR assay was 5 copies/reaction for RSV, HRV and HMPV, respectively, and no cross-reaction with other common respiratory viruses was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.51 to 3.67%. Of 398 nasopharyngeal aspirates samples tested, 109 (27.39%), 150 (37.69%) and 44 (11.06%) were positive for RSV, HRV and HMPV, respectively, whereas 95 (23.87%), 137 (34.42%) and 38 (9.55%) were positive for RSV, HRV and HMPV, respectively, by individual RT-qPCR assay. Thirty three samples that were positive by mOTNRT-PCR but negative by RT-qPCR were confirmed as true positives by sequencing using reported traditional two-step nested PCR assay.
CONCLUSION
mOTNRT-PCR assay reveals extremely higher sensitivity than that of RT-qPCR assay for detecting RSV, HRV and HMPV in clinical settings.
Topics: Acute Disease; Child; Child, Preschool; Female; Humans; Infant; Male; Metapneumovirus; Multiplex Polymerase Chain Reaction; Nasopharynx; Paramyxoviridae Infections; Picornaviridae Infections; Reproducibility of Results; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Rhinovirus; Sensitivity and Specificity
PubMed: 30376870
DOI: 10.1186/s12985-018-1061-0 -
Reviews in Medical Virology Jul 2021Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self-limiting, but may also be associated... (Review)
Review
Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self-limiting, but may also be associated with bronchiolitis in infants, pneumonia in the immunocompromised and exacerbation in patients with pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Viral infection accounts for as many as two thirds of asthma exacerbations in children and more than half in adults. Allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. The prevalence of RV-induced wheezing will likely continue to increase given that asthma affects a significant proportion of the population, with allergic asthma accounting for the majority. Several new respiratory viruses and their subgroups have been discovered, with various degrees of relevance. This review will focus on RV infection in the context of the epidemiologic evidence, genetic variability, pathobiology, clinical studies in the context of asthma, differences with other viruses including COVID-19 and current treatment interventions.
Topics: Asthma; Common Cold; Genetic Variation; Humans; Picornaviridae Infections; Rhinovirus
PubMed: 33217098
DOI: 10.1002/rmv.2193 -
Viruses Nov 2022While the aetiology of asthma is unclear, the onset and/or exacerbation of asthma may be associated with respiratory infections. Virus-induced asthma is also known as... (Review)
Review
While the aetiology of asthma is unclear, the onset and/or exacerbation of asthma may be associated with respiratory infections. Virus-induced asthma is also known as virus-associated/triggered asthma, and the reported main causative agent is rhinovirus (RV). Understanding the relationship between viral infections and asthma may overcome the gaps in deferential immunity between viral infections and allergies. Moreover, understanding the complicated cytokine networks involved in RV infection may be necessary. Therefore, the complexity of RV-induced asthma is not only owing to the response of airway and immune cells against viral infection, but also to allergic immune responses caused by the wide variety of cytokines produced by these cells. To better understand RV-induced asthma, it is necessary to elucidate the nature RV infections and the corresponding host defence mechanisms. In this review, we attempt to organise the complexity of RV-induced asthma to make it easily understandable for readers.
Topics: Humans; Rhinovirus; Picornaviridae Infections; Asthma; Cytokines; Enterovirus Infections; Hypersensitivity
PubMed: 36560620
DOI: 10.3390/v14122616 -
Viruses Apr 2021Rhinoviruses (RVs) are the etiological agents of upper respiratory tract infections, particularly the common cold. Infections in the lower respiratory tract is shown to... (Review)
Review
Rhinoviruses (RVs) are the etiological agents of upper respiratory tract infections, particularly the common cold. Infections in the lower respiratory tract is shown to cause severe disease and exacerbations in asthma and COPD patients. Viruses being obligate parasites, hijack host cell pathways such as programmed cell death to suppress host antiviral responses and prolong viral replication and propagation. RVs are non-enveloped positive sense RNA viruses with a lifecycle fully contained within the cytoplasm. Despite decades of study, the details of how RVs exit the infected cell are still unclear. There are some diverse studies that suggest a possible role for programmed cell death. In this review, we aimed to consolidate current literature on the impact of RVs on cell death to inform future research on the topic. We searched peer reviewed English language literature in the past 21 years for studies on the interaction with and modulation of cell death pathways by RVs, placing it in the context of the broader knowledge of these interconnected pathways from other systems. Our review strongly suggests a role for necroptosis and/or autophagy in RV release, with the caveat that all the literature is based on RV-A and RV-B strains, with no studies to date examining the interaction of RV-C strains with cell death pathways.
Topics: Autophagy; Cell Death; Humans; Necroptosis; Picornaviridae Infections; Rhinovirus; Virus Replication
PubMed: 33916958
DOI: 10.3390/v13040629 -
Chest May 2019Human rhinoviruses (RVs) are picornaviruses that can cause a variety of upper and lower respiratory tract illnesses, including the common cold, bronchitis, pneumonia,... (Review)
Review
Human rhinoviruses (RVs) are picornaviruses that can cause a variety of upper and lower respiratory tract illnesses, including the common cold, bronchitis, pneumonia, and exacerbations of chronic respiratory diseases such as asthma. There are currently > 160 known types of RVs classified into three species (A, B, and C) that use three different cellular membrane glycoproteins expressed in the respiratory epithelium to enter the host cell. These viral receptors are intercellular adhesion molecule 1 (used by the majority of RV-A and all RV-B types), low-density lipoprotein receptor family members (used by 12 RV-A types), and cadherin-related family member 3 (CDHR3; used by RV-C). RV-A and RV-B interactions with intercellular adhesion molecule 1 and low-density lipoprotein receptor glycoproteins are well defined and their cellular functions have been described, whereas the mechanisms of the RV-C interaction with CDHR3 and its cellular functions are being studied. A single nucleotide polymorphism (rs6967330) in CDHR3 increases cell surface expression of this protein and, as a result, also promotes RV-C infections and illnesses. There are currently no approved vaccines or antiviral therapies available to treat or prevent RV infections, which is a major unmet medical need. Understanding interactions between RV and cellular receptors could lead to new insights into the pathogenesis of respiratory illnesses as well as lead to new approaches to control respiratory illnesses caused by RV infections.
Topics: Host Microbial Interactions; Humans; Picornaviridae Infections; Receptors, Virus; Rhinovirus
PubMed: 30659817
DOI: 10.1016/j.chest.2018.12.012 -
F1000Research 2018Rhinoviruses are the most common cause of upper respiratory tract infections. However, they can induce exacerbations of chronic obstructive pulmonary disease and asthma,... (Review)
Review
Rhinoviruses are the most common cause of upper respiratory tract infections. However, they can induce exacerbations of chronic obstructive pulmonary disease and asthma, bronchiolitis in infants, and significant lower respiratory tract infections in children, the immunosuppressed, and the elderly. The large number of rhinovirus strains (currently about 160) and their antigenic diversity are significant obstacles in vaccine development. The phenotype of immune responses induced during rhinovirus infection can affect disease severity. Recognition of rhinovirus and a balance of innate responses are important factors in rhinovirus-induced morbidity. Immune responses to rhinovirus infections in healthy individuals are typically of the T helper type 1 (Th1) phenotype. However, rhinovirus-driven asthma exacerbations are additionally characterised by an amplified Th2 immune response and airway neutrophilia. This commentary focuses on recent advances in understanding immunity toward rhinovirus infection and how innate and adaptive immune responses drive rhinovirus-induced asthma exacerbations.
Topics: Adaptive Immunity; Asthma; Humans; Immunity, Innate; Picornaviridae Infections; Rhinovirus; Th1 Cells; Th2 Cells
PubMed: 30345002
DOI: 10.12688/f1000research.15337.1