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Der Internist Nov 2019Human rhinoviruses (RV) belong to the Picornaviridae and are divided into three species: rhinovirus A, B and C. As causative viruses of upper airway infections... (Review)
Review
Human rhinoviruses (RV) belong to the Picornaviridae and are divided into three species: rhinovirus A, B and C. As causative viruses of upper airway infections (common cold), they possess enormous epidemiological and clinical importance. Furthermore, rhinoviruses are significant pathogens of acute exacerbations of chronic airway diseases such as asthma and chronic obstructive pulmonary disease. Their role as a cofactor in the development of pneumonia and their relevance in critically ill patients is still unclear and the focus of current research. Due to the unspecific clinical symptoms, diagnosis is difficult. Laboratory detection is sophisticated and a distinction between clinically relevant infection and contamination not always possible. Specific therapeutic antiviral strategies against rhinovirus infection do not exist as yet and, due to the large variety of subtypes, the development of vaccines remains a considerable challenge.
Topics: Antiviral Agents; Asthma; Disease Progression; Humans; Picornaviridae Infections; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinitis; Rhinovirus
PubMed: 31463521
DOI: 10.1007/s00108-019-00672-4 -
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 -
Immunity, Inflammation and Disease Mar 2018Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic... (Clinical Trial)
Clinical Trial
BACKGROUND
Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined.
OBJECTIVE
The aim of this study was to characterize and compare T-cell responses between RV-A and RV-C and to test the hypothesis that T-cell responses would differ between asthmatic children and healthy controls.
METHODS
A multi-parameter flow cytometry assay was used to characterize the in vitro recall T-cell response against RV-A and RV-C in PBMCs from children with acute asthma (n = 22) and controls (n = 26). The responses were induced by pools of peptides containing species-specific VP1 epitopes of RV-A and RV-C.
RESULTS
Regardless of children's clinical status, all children that responded to the in vitro stimulation (>90%) had a similar magnitude of CD4+ T-cell responses to RV-A and RV-C. However, asthmatic children had a significantly lower number of circulating regulatory T cells (Tregs), and healthy controls had significantly more Tregs induced by RV-A than RV-C.
CONCLUSIONS AND CLINICAL RELEVANCE
The comparable recall memory T-cell responses in asthmatic and control children to both RV-A and RV-C show that differences in the antibody and inflammatory responses previously described are likely to be due to regulation, with a demonstrated candidate being reduced regulatory T-cells. The reduced Treg numbers demonstrated here could explain the asthmatic's inability to appropriately control immunopathological responses to RV infections.
Topics: Adolescent; Asthma; Child; Child, Preschool; Coxsackievirus Infections; Enterovirus; Female; Humans; Immunologic Memory; Infant; Male; T-Lymphocytes, Regulatory
PubMed: 29124902
DOI: 10.1002/iid3.206 -
Methods in Molecular Biology (Clifton,... 2015Infectivity is a fundamental property of viral pathogens such as human rhinoviruses (HRVs). This chapter describes two methods for measuring the infectivity of HRV-A and...
Infectivity is a fundamental property of viral pathogens such as human rhinoviruses (HRVs). This chapter describes two methods for measuring the infectivity of HRV-A and -B serotypes: end point dilution (TCID50) assay and plaque assay. End point dilution assay is a quantal, not quantitative, assay that determines the dilution of the sample at which 50 % of the aliquots have infectious virus. It can be used for all the HRV-A and -B serotypes and related clinical isolates that grow in cell culture and induce cytopathic effect (CPE), degenerative changes in cells that are visible under a microscope. Plaque assay is a quantitative assay that determines the number of infectious units of a virus in a sample. After an infectious unit of virus infects one cell, the infected cell produces progeny viruses that then infect and kill a circle of adjacent cells. This circle of dead cells detaches from the dish and thus leaves a clear hole in a cell monolayer. Plaque assay works only for HeLa-adapted HRV-A and -B serotypes that can make visible plaques on the cell monolayer. Currently the end point dilution assay and plaque assay have not been developed for the newly discovered HRV-C.
Topics: Cell Line; Cryopreservation; HeLa Cells; Humans; Rhinovirus; Serogroup; Viral Plaque Assay
PubMed: 25261308
DOI: 10.1007/978-1-4939-1571-2_7 -
Viruses Aug 2022Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite...
Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite important evidence on the role of RV reported by clinicians and life scientists, there are still unanswered questions regarding their influence on asthma exacerbation in young patients. Thus, we measured the RVspecies-specific IgG titers in our German pediatric exacerbation cohort using a microarray-based technology. For this approach, human sera of patients with exacerbated asthma and wheeze, as well as healthy control subjects ( = 136) were included, and correlation analyses were performed. Concordantly with previously published results, we observed significantly higher cumulative levels of RV species A-specific IgG ( = 0.011) and RV-C-specific IgG ( = 0.051) in exacerbated asthma group compared to age-matched controls. Moreover, atopic wheezers had increased RV-specific IgG levels for species A ( = 0.0011) and species C ( = 0.0009) compared to non-atopic wheezers. Hypothesizing that bacterial infection positively correlates with immune memory against RV, we included nasopharyngeal swab results in our analyses and detected limited correlations. Interestingly, the eosinophil blood titer positively correlated with RV-specific IgG levels. With these observations, we add important observations to the existing data regarding exacerbation in pediatric and adolescent medicine. We propose that scientists and clinicians should pay more attention to the relevance of RV species in susceptible pediatric patients.
Topics: Adolescent; Antibody Formation; Asthma; Child; Enterovirus Infections; Humans; Immunoglobulin G; Picornaviridae Infections; Rhinovirus
PubMed: 36146664
DOI: 10.3390/v14091857 -
Viruses Mar 2023Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and...
Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air-liquid interface (ALI). After AECs were infected with RV-A16, PI reduced the viral RNA copy number by 70% and downregulated (55-75%) the expression of antiviral (MDA5, IRF7, and IFN-lambda) and CXCL11 chemokine genes. In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50-80%) IL6 gene expression and protein secretion and CXCL11 protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection alone in AECs. The observed inhibitory effects were indirect and resulted mainly from the inhibition of virus replication. Cell-type enrichment analysis of viral-regulated genes opposed by PI treatment revealed the PI-inhibited viral induction of goblet cell metaplasia and the virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, the PI treatment also altered the ability of RV-A16 to regulate the expression of some phosphatidylinositol 4-kinase (); acyl-CoA-binding, domain-containing (); and low-density lipoprotein receptor () genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic, antiviral agent for RV infection prophylaxis and treatment.
Topics: Humans; Pulmonary Surfactants; Rhinovirus; Epithelial Cells; Epithelium; Antiviral Agents; Enterovirus Infections; Lung; Lipids; Picornaviridae Infections
PubMed: 36992456
DOI: 10.3390/v15030747 -
Frontiers in Cellular and Infection... 2022Rhinovirus causes many types of respiratory illnesses, ranging from minor colds to exacerbations of asthma. is an opportunistic pathogen that is increased in abundance...
Rhinovirus causes many types of respiratory illnesses, ranging from minor colds to exacerbations of asthma. is an opportunistic pathogen that is increased in abundance during rhinovirus illnesses and asthma exacerbations and is associated with increased severity of illness through mechanisms that are ill-defined. We used a co-infection model of human airway epithelium differentiated at the air-liquid interface to test the hypothesis that rhinovirus infection promotes adhesion and survival on the respiratory epithelium. Initial experiments showed that infection with alone did not damage the epithelium or induce cytokine production, but increased trans-epithelial electrical resistance, indicative of increased barrier function. In a co-infection model, infection with the more virulent rhinovirus-A and rhinovirus-C, but not the less virulent rhinovirus-B types, increased cell-associated . Immunofluorescent staining demonstrated that adhered to rhinovirus-infected ciliated epithelial cells and infected cells being extruded from the epithelium. Rhinovirus induced pronounced changes in gene expression and secretion of inflammatory cytokines. In contrast, caused minimal effects and did not enhance RV-induced responses. Our results indicate that rhinovirus-A or C infection increases survival and cell association while infection alone does not cause cytopathology or epithelial inflammation. Our findings suggest that rhinovirus and co-infection could promote epithelial damage and more severe illness by amplifying leukocyte inflammatory responses at the epithelial surface.
Topics: Humans; Moraxella catarrhalis; Rhinovirus; Coinfection; Respiratory Mucosa; Asthma; Epithelial Cells; Enterovirus Infections
PubMed: 36733852
DOI: 10.3389/fcimb.2022.1060748 -
American Journal of Respiratory and... Jul 2020Individuals with asthma have heightened antibody responses to rhinoviruses (RVs), although those specific for RV-C are lower than responses specific for RV-A,... (Comparative Study)
Comparative Study
Individuals with asthma have heightened antibody responses to rhinoviruses (RVs), although those specific for RV-C are lower than responses specific for RV-A, suggesting poor immunity to this species. To ascertain and compare T-cell memory responses induced by RV-A and RV-C in children with and without asthma. Peripheral blood mononuclear cells from 17 children with asthma and 19 control subjects without asthma were stimulated with peptide formulations to induce representative species-specific responses to RV-A and RV-C. Molecular profiling (RNA sequencing) was used to identify enriched pathways and upstream regulators. Responses to RV-A showed higher expression of IFNG and STAT1 compared with RV-C, and significant expression of CXCL9, 10, and 11 was not found for RV-C. There was no reciprocal increase of T-helper cell type 2 (Th2) cytokine genes or the Th2 chemokine genes CCL11, CCL17, and CCL22. RV-C induced higher expression of CCL24 (eotaxin-2) than RV-A in the responses of children with and without asthma. Upstream regulator analysis showed both RV-A and, although to a lesser extent, RV-C induced predominant Th1 and inflammatory cytokine expression. The responses of children with asthma compared with those without asthma were lower for both RV-A and RV-C while retaining the pattern of gene expression and upstream regulators characteristic of each species. All groups showed activation of the IL-17A pathway. RV-C induced memory cells with a lower IFN-γ-type response than RV-A without T-helper cell type 2 (Th2) upregulation. Children with asthma had lower recall responses than those without asthma while largely retaining the same gene activation profile for each species. RV-A and RV-C, therefore, induce qualitatively different T-cell responses.
Topics: Adolescent; Asthma; Cells, Cultured; Child; Child, Preschool; Enterovirus; Female; Gene Expression Regulation, Viral; Healthy Volunteers; Humans; Lymphocytes; Male; Picornaviridae Infections; Th2 Cells
PubMed: 32142615
DOI: 10.1164/rccm.201908-1670OC -
Journal of Medical Virology Apr 2017Human rhinovirus (RV) is commonly associated with severe acute lower respiratory infections (ALRI) in children. We aimed to describe the distribution of RV species and...
Human rhinovirus (RV) is commonly associated with severe acute lower respiratory infections (ALRI) in children. We aimed to describe the distribution of RV species and associations between RV species and clinical features in children hospitalized with clinically severe pneumonia (CSP) in Morocco. Nasopharyngeal aspirates (NPAs) were collected from 700 children, 2-59 months of age, admitted with CSP to the Hôpital d'Enfants de Rabat in Morocco. At least one respiratory virus was identified in 92% of children, of which RV was the most common (53%). PCR assays, sequencing, and phylogenetic tree analyses were carried out on 183 RV-positive NPAs to determine RV species and genotypes. Of 157 successfully genotyped NPAs, 60 (38.2%) were RV-A, 8 (5.1%) were RV-B, and 89 (56.7%) were RV-C. Wheezing and cyanosis were more common in RV-C-positive than RV-A-positive children (80.9% vs. 56.7%; P = 0.001 for wheezing and 10.1% vs. 0%; P = 0.011 for cyanosis). Physician's discharge diagnosis of pneumonia was more frequent among RV-A-positive (40.0%) than RV-C-positive children (20.2%; P = 0.009). RV-A and RV-C showed distinct seasonal patterns. Our findings suggest that RV-C is associated with wheezing illness while RV-A is associated with pneumonia. J. Med. Virol. 89:582-588, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Asthma; Child, Preschool; Cyanosis; Female; Genotype; Hospitalization; Humans; Infant; Male; Morocco; Nasopharynx; Phylogeny; Picornaviridae Infections; Pneumonia, Viral; Polymerase Chain Reaction; RNA, Viral; Respiratory Sounds; Rhinovirus; Sequence Analysis, DNA
PubMed: 27677921
DOI: 10.1002/jmv.24684 -
Open Forum Infectious Diseases Dec 2021Rhinoviruses (RVs) are ubiquitous pathogens and the principal etiological agents of common cold. Despite the high frequency of RV infections, data describing their...
BACKGROUND
Rhinoviruses (RVs) are ubiquitous pathogens and the principal etiological agents of common cold. Despite the high frequency of RV infections, data describing their long-term epidemiological patterns in a defined population remain limited.
METHODS
Here, we analyzed 1070 VP4/VP2 genomic region sequences sampled at Kilifi County Hospital on the Kenya coast. The samples were collected between 2007 and 2018 from hospitalized pediatric patients (<60 months of age) with acute respiratory illness.
RESULTS
Of 7231 children enrolled, RV was detected in 1497 (20.7%) and VP4/VP2 sequences were recovered from 1070 samples (71.5%). A total of 144 different RV types were identified (67 , 18 , and 59 ) and at any month, several types co-circulated with alternating predominance. Within types, multiple genetically divergent variants were observed. Ongoing RV infections through time appeared to be a combination of (1) persistent types (observed up to 7 consecutive months), (2) reintroduced genetically distinct variants, and (3) new invasions (average of 8 new types annually).
CONCLUSIONS
Sustained RV presence in the Kilifi community is mainly due to frequent invasion by new types and variants rather than continuous transmission of locally established types/variants.
PubMed: 34988244
DOI: 10.1093/ofid/ofab571