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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 -
American Journal of Respiratory and... Jul 2020
Topics: Asthma; Child; Enterovirus; Humans; Lymphocytes; Picornaviridae Infections; Rhinovirus
PubMed: 32240597
DOI: 10.1164/rccm.202003-0634ED -
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 -
Canadian Respiratory Journal 2022Human rhinovirus (HRV) can lead to a variety of respiratory illnesses; it is also an uncommon cause of community-acquired pneumonia (CAP). We described the...
INTRODUCTION
Human rhinovirus (HRV) can lead to a variety of respiratory illnesses; it is also an uncommon cause of community-acquired pneumonia (CAP). We described the characteristics and outcomes of patients hospitalized for CAP due to HRV.
METHODS
We retrospectively studied consecutive adult patients admitted to King Abdulaziz Medical City-Riyadh with CAP due to HRV between 2016 and 2019. The diagnosis was made by respiratory multiplex PCR within 48 hours of hospitalization. We compared patients requiring ICU admission to those who did not.
RESULTS
One-hundred-and-six patients were studied (peak hospitalization between November and January, median age 71.5 years, hypertension 59%, diabetes 50%, and chronic respiratory disease 44.3%); 16 (15.1%) patients required ICU admission. The median pneumonia severity index score (PSI) was 107, with no significant difference between ICU and nonICU patients. ICU patients had a higher prevalence of tachypnea (62.5% vs. 26.7%, =0.005), hemoptysis (12.5% vs 0%, =0.001), and lymphopenia (71.4% vs 26.3%, =0.01). Chest X-ray on presentation showed bilateral infiltrates in 47/101 (46.5%) patients and unilateral infiltrates in 26/101 (25.7%) patients. Systemic corticosteroids were used in 54.7% of patients (the median initial dose was 120 mg of prednisone equivalent and was higher in nonICU patients). Most (69.2%) ICU patients received mechanical ventilation (median duration of 8 days). Bacterial coinfection (6.6%) and superinfection (3.8%) were rare. The overall hospital mortality was 9.4% (higher for ICU patients: 37.5% vs. 4.4%, < 0.001).
CONCLUSIONS
Most patients with CAP due to HRV were elderly and had significant comorbidities. ICU admission was required in almost one in six patients and was associated with higher mortality.
Topics: Adult; Humans; Aged; Retrospective Studies; Rhinovirus; Intensive Care Units; Severity of Illness Index; Community-Acquired Infections; Pneumonia; Hospitalization
PubMed: 36531535
DOI: 10.1155/2022/1349994 -
Whole genome sequencing of two human rhinovirus A types (A101 and A15) detected in Kenya, 2016-2018.Wellcome Open Research 2021Virus genome sequencing is increasingly utilized in epidemiological surveillance. Genomic data allows comprehensive evaluation of underlying viral diversity and...
Virus genome sequencing is increasingly utilized in epidemiological surveillance. Genomic data allows comprehensive evaluation of underlying viral diversity and epidemiology to inform control. For human rhinovirus (HRV), genomic amplification and sequencing is challenging due to numerous types, high genetic diversity and inadequate reference sequences. We developed a tiled amplicon type-specific protocol for genome amplification and sequencing on the Illumina MiSeq platform of two HRV types, A15 and A101. We then assessed added value in analyzing whole genomes relative to the VP4/2 region only in the investigation of HRV molecular epidemiology within the community in Kilifi, coastal Kenya. We processed 73 nasopharyngeal swabs collected between 2016-2018, and 48 yielded at least 70% HRV genome coverage. These included all A101 samples (n=10) and 38 (60.3%) A15 samples. Phylogenetic analysis revealed that the Kilifi A101 sequences interspersed with global A101 genomes available in GenBank collected between 1999-2016. On the other hand, our A15 sequences formed a monophyletic group separate from the global genomes collected in 2008 and 2019. An improved phylogenetic resolution was observed with the genome phylogenies compared to the VP4/2 phylogenies. We present a type-specific full genome sequencing approach for obtaining HRV genomic data and characterizing infections.
PubMed: 34522789
DOI: 10.12688/wellcomeopenres.16911.2 -
FASEB Journal : Official Publication of... Jan 2021Human Rhinovirus (HRV) is a major cause of common cold, bronchiolitis, and exacerbations of chronic pulmonary diseases such as asthma. CD8 T cell responses likely play...
Human Rhinovirus (HRV) is a major cause of common cold, bronchiolitis, and exacerbations of chronic pulmonary diseases such as asthma. CD8 T cell responses likely play an important role in the control of HRV infection but, surprisingly, HRV-specific CD8 T cell epitopes remain yet to be identified. Here, we approached the discovery and characterization of conserved HRV-specific CD8 T cell epitopes from species A (HRV A) and C (HRV C), the most frequent subtypes in the clinics of various pulmonary diseases. We found IFNγ-ELISPOT positive responses to 23 conserved HRV-specific peptides on peripheral blood mononuclear cells (PBMCs) from 14 HLA I typed subjects. Peptide-specific IFNγ production by CD8 T cells and binding to the relevant HLA I were confirmed for six HRV A-specific and three HRV C-specific CD8 T cell epitopes. In addition, we validated A*02:01-restricted epitopes by DimerX staining and found out that these peptides mediated cytotoxicity. All these A*02:01-restricted epitopes were 9-mers but, interestingly, we also identified and validated an unusually long 16-mer epitope peptide restricted by A*02:01, HRVC (GLEPLDLNTSAGFPYV). HRV-specific CD8 T cell epitopes describe here are expected to elicit CD8 T cell responses in up to 87% of the population and could be key for developing an HRV vaccine.
Topics: CD8-Positive T-Lymphocytes; Enterovirus; Epitopes, T-Lymphocyte; Female; HLA-A2 Antigen; Humans; Male; Peptides; Picornaviridae Infections; Viral Proteins
PubMed: 33230881
DOI: 10.1096/fj.202002165R -
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 -
Cureus Mar 2022The occurrence of rhabdomyolysis in pediatric patients is considered a rare complication that can follow certain viral infections in a syndrome better defined as...
The occurrence of rhabdomyolysis in pediatric patients is considered a rare complication that can follow certain viral infections in a syndrome better defined as virus-associated rhabdomyolysis. In this research, we will present the case of a ten-year-old male patient who presented to the emergency department with chief complaints of severe bilateral leg pain and inability to walk. Furthermore, the patient complained of dysphagia for both solid and liquid along with dark-colored urine. Initial investigations showed an increase in creatine kinase (CK), C-reactive protein (CRP), and liver enzymes. Additionally, urine analysis was obtained with positive traces of blood, protein, and white blood cell. X-ray was ordered with no significant finding. Finally, the diagnosis was reached in accordance to the results of the respiratory panel multiplex (PCR) as the third case of rhinovirus-induced rhabdomyolysis. He was treated with isotonic intravenous fluids, and he was discharged on hospital day 20 with a CK of 2062 IU/L. The patient was discharged fully recovered, was able to stand and walk alone, and with no complications. In this third to be reported case of rhinovirus-induced rhabdomyolysis, we aim to increase the knowledge among the general pediatric field regarding the possible presentation and treatment of any similar case.
PubMed: 35371843
DOI: 10.7759/cureus.22784 -
Virus Research Jan 2023Human rhinovirus (HRV), the main etiologic agent of the common cold, is responsible for significant morbidity, medical costs, and the loss of productivity in the...
Human rhinovirus (HRV), the main etiologic agent of the common cold, is responsible for significant morbidity, medical costs, and the loss of productivity in the workplace and school. To prevent the spread of HRV, accurate, low-cost and rapid diagnostics of HRV is crucial for identifying those at-risk for the illness associated with HRV, with the most frequently detected species, including HRV species A (HRV-A) and C (HRV-C). Here, a novel HRV-A and/or HRV-C molecular diagnostic assay that integrates reverse-transcription recombinase polymerase amplification assay (RT-RPA) amplification with CRISPR/Cas12a detection, with the result readout using a fluorescence detector or lateral flow strip (LFS). The established assay could be completed within 50 min without complex instruments and skilled technicians. The limit of detection of the RT-RPA-Cas12a-mediated real-time fluorescence or LFS assay could reach 0.1 copy/μl, and 0.5 copy/μl for the end-point fluorescence assay with a UV light illuminator readout, respectively. Meanwhile, the assay demonstrates excellent specificity without cross-reactivity to non-target viruses. Furthermore, they were appraised using 80 clinical samples, and RT-RPA-Cas12a-mediated fluorescence or LFS assay displayed high-accuracy with positive and negative predictive agreement of 96.7%, 95% and 100%, respectively. Taken together, the RT-RPA-Cas12a-mediated assay is a rapid, sensitive, and specific detection tool for routine and on-site detection method for HRV-A and/or HRV-C infections, and shows great promise for use in resource-poor or constrained settings.
PubMed: 36375713
DOI: 10.1016/j.virusres.2022.199001 -
Archives of Virology Apr 2022Human rhinoviruses (HRVs) cause acute upper and lower respiratory tract infections and aggravation of asthma and chronic obstructive pulmonary disease. The 5'...
Human rhinoviruses (HRVs) cause acute upper and lower respiratory tract infections and aggravation of asthma and chronic obstructive pulmonary disease. The 5' untranslated region (5' UTR) and the VP4/VP2 region are widely used for genotyping of HRVs. Members of the species Rhinovirus A and Rhinovirus C have been reported to be more frequently associated with severe disease than members of the species Rhinovirus B. We report the clinical and molecular epidemiological characteristics of HRVs circulating from 2012 to 2020 in Shanghai. A total of 5832 nasopharyngeal swabs from patients with acute respiratory infections were collected. A real-time reverse transcription polymerase chain reaction assay was used for virus detection. The 5' untranslated region and VP4/VP2 region were amplified and sequenced for genotyping and phylogenetic analysis. The overall rate of rhinovirus detection was 2.74% (160/5832), with members of species A, B, and C accounting for 68.13% (109/160), 20.00% (32/160), and 11.88% (19/160) of the total, respectively. A peak of HRV infection was observed in autumn (5.34%, 58/1087). Patients in the 3- to 14-year-old age group were the most susceptible to HRV infection (χ = 23.88, P = 0.017). Influenza virus and Streptococcus pneumoniae were detected more frequently than other pathogens in cases of coinfection. Recombination events were identified in 10 strains, which were successfully genotyped by phylogenetic analysis based on the 5' UTR-VP4/VP2 region but not the 5' UTR region alone. We observed a high degree of variability in the relative distribution of HRV genotypes and the prevalence of HRV infection in Shanghai and found evidence of recombination events in the portion of the genome containing the 5' UTR and the VP4/VP2 region between HRV-C strains and HRV-A-like strains. This study is important for surveillance of the spread of HRVs and the emergence of new variants.
Topics: Adolescent; Child; Child, Preschool; China; Humans; Molecular Epidemiology; Phylogeny; Picornaviridae Infections; Rhinovirus
PubMed: 35303167
DOI: 10.1007/s00705-022-05405-x