Viruses

Research

Jump to: Review

18 pages, 3536 KiB

Open AccessArticle

Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium

by Mari Numata, Satria Sajuthi, Yury A. Bochkov, Jessica Loeffler, Jamie Everman, Eszter K. Vladar, Riley A. Cooney, Richard Lee Reinhardt, Andrew H. Liu, Max A. Seibold and Dennis R. Voelker

Viruses 2023, 15(3), 747; https://doi.org/10.3390/v15030747 - 14 Mar 2023

Cited by 6 | Viewed by 2526

Abstract

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 [...] Read more.

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 (PI4K); acyl-CoA-binding, domain-containing (ACBD); and low-density lipoprotein receptor (LDLR) 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. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

19 pages, 2227 KiB

Open AccessArticle

Analysis of Exosomal MicroRNA Dynamics in Response to Rhinovirus Challenge in a Longitudinal Case-Control Study of Asthma

by Wangfei Wang, Anirban Sinha, René Lutter, Jie Yang, Christian Ascoli, Peter J. Sterk, Nicole K. Nemsick, David L. Perkins and Patricia W. Finn

Viruses 2022, 14(11), 2444; https://doi.org/10.3390/v14112444 - 3 Nov 2022

Cited by 5 | Viewed by 2127

Abstract

Asthma symptoms are often exacerbated by the common-cold-causing rhinovirus (RV). In this study, we characterized the temporal behavior of circulating exosomal microRNAs (ExoMiRNAs) in a longitudinal bi-phasic case-control study of mild asthmatics (n = 12) and matched non-atopic healthy controls (n [...] Read more.

Asthma symptoms are often exacerbated by the common-cold-causing rhinovirus (RV). In this study, we characterized the temporal behavior of circulating exosomal microRNAs (ExoMiRNAs) in a longitudinal bi-phasic case-control study of mild asthmatics (n = 12) and matched non-atopic healthy controls (n = 12) inoculated with rhinovirus. We aimed to define clinical and immunologic characteristics associated with differentially expressed (DE) miRNAs. In total, 26 DE ExoMiRNAs, including hsa-let-7f-5p, hsa-let-7a-5p, hsa-miR-122-5p, hsa-miR-101-3p, and hsa-miR-126-3p, were identified between asthmatic and healthy subjects after inoculation with RV. Time series clustering identified a unique Cluster of Upregulated DE ExoMiRNAs with augmenting mean expression and a distinct Cluster of Downregulated DE ExoMiRNAs with mean expression decline in asthmatic subjects upon RV challenge. Notably, the Upregulated Cluster correlated with Th1 and interferon-induced cytokines/chemokines (IFN-

γ

and IFN-

γ

-inducible protein-10) and interleukin-10 (IL-10). Conversely, the Downregulated Cluster correlated with IL-13, a Th2 cytokine, pulmonary function measurements (FVC%, FEV1%, and PEF%), and inflammatory biomarkers (FeNO, eosinophil%, and neutrophil%). Key ExoMiRNA–target gene and anti-viral defense mechanisms of the Upregulated and Downregulated Clusters were identified by network and gene enrichment analyses. Our findings provide insight into the regulatory role of ExoMiRNAs in RV-induced asthma. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

15 pages, 2583 KiB

Open AccessEditor’s ChoiceArticle

IL-33 Induces an Antiviral Signature in Mast Cells but Enhances Their Permissiveness for Human Rhinovirus Infection

by Charlene Akoto, Anna Willis, Chiara F. Banas, Joseph A. Bell, Dean Bryant, Cornelia Blume, Donna E. Davies and Emily J. Swindle

Viruses 2022, 14(11), 2430; https://doi.org/10.3390/v14112430 - 1 Nov 2022

Cited by 4 | Viewed by 2832

Abstract

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway [...] Read more.

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

15 pages, 2360 KiB

Open AccessArticle

Microarray-Based Analyses of Rhinovirus Species-Specific Antibody Responses in Exacerbated Pediatric Asthma in a German Pediatric Cohort

by Erwan Sallard, Katarzyna Niespodziana, Maja Bajic, Thomas Schlederer, Peter Errhalt, Ann-Kathrin Behrendt, Stefan Wirth, Almut Meyer-Bahlburg, Anja Ehrhardt, Rudolf Valenta and Malik Aydin

Viruses 2022, 14(9), 1857; https://doi.org/10.3390/v14091857 - 24 Aug 2022

Cited by 3 | Viewed by 1940

Abstract

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 [...] Read more.

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 (n = 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 (p = 0.011) and RV-C-specific IgG (p = 0.051) in exacerbated asthma group compared to age-matched controls. Moreover, atopic wheezers had increased RV-specific IgG levels for species A (p = 0.0011) and species C (p = 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. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

14 pages, 2433 KiB

Open AccessArticle

Human Rhinoviruses in Pediatric Patients in a Tertiary Care Hospital in Germany: Molecular Epidemiology and Clinical Significance

by Franziska Neugebauer, Sandra Bergs, Uwe Gerd Liebert and Mario Hönemann

Viruses 2022, 14(8), 1829; https://doi.org/10.3390/v14081829 - 20 Aug 2022

Cited by 3 | Viewed by 2096

Abstract

Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in pediatric patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient [...] Read more.

Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in pediatric patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of pediatric RV infections. In total, the respiratory specimens of 776 patients (<18 years), collected from 2013 to 2017, were analyzed. Infections occurred throughout the entire year, with peaks occurring in fall and winter, and showed remarkably high intra- and interseasonal diversity for RV genotypes. RV species were detected in the following frequencies: 49.1% RV-A, 5.9% RV-B, and 43.6% RV-C. RV-C was found to be more frequently associated with asthma (p = 0.04) and bronchiolitis (p < 0.001), while RV-A was more frequently associated with fever (p = 0.001) and pneumonia (p = 0.002). Additionally, 35.3% of the patients had co-infections with other pathogens, which were associated with a longer hospital stay (p < 0.001), need for ventilation (p < 0.001), and pneumonia (p < 0.001). Taken together, this study shows pronounced RV genetic diversity in pediatric patients and indicates differences in RV-associated pathologies, as well as an important role for co-infections. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

16 pages, 2351 KiB

Open AccessArticle

Viral Infection and Respiratory Exacerbation in Children: Results from a Local German Pediatric Exacerbation Cohort

by Erwan Sallard, Frank Schult, Carolin Baehren, Eleni Buedding, Olivier Mboma, Parviz Ahmad-Nejad, Beniam Ghebremedhin, Anja Ehrhardt, Stefan Wirth and Malik Aydin

Viruses 2022, 14(3), 491; https://doi.org/10.3390/v14030491 - 27 Feb 2022

Cited by 7 | Viewed by 2861

Abstract

Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the [...] Read more.

Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the early phase. Only a limited number of international exacerbation cohorts were studied. Here, we have established a local pediatric exacerbation study in Germany consisting of children with asthma or chronic, recurrent bronchitis and analyzed the viriome within the nasopharyngeal swab specimens derived from the entire cohort (n = 141). Interestingly, 41% of exacerbated children had a positive test result for human rhinovirus (HRV)/human enterovirus (HEV), and 14% were positive for respiratory syncytial virus (RSV). HRV was particularly prevalent in asthmatics (56%), wheezers (50%), and atopic (66%) patients. Lymphocytes were decreased in asthmatics and in HRV-infected subjects, and patients allergic to house dust mites were more susceptible to HRV infection. Our study thus confirms HRV infection as a strong ‘biomarker’ of exacerbated asthma. Further longitudinal studies will show the clinical progress of those children with a history of an RSV or HRV infection. Vaccination strategies and novel treatment guidelines against HRV are urgently needed to protect those high-risk children from a serious course of disease. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

Review

Jump to: Research

11 pages, 473 KiB

Open AccessReview

Rhinovirus Infection and Virus-Induced Asthma

by Yuriko Hayashi, Mitsuru Sada, Tatsuya Shirai, Kaori Okayama, Ryusuke Kimura, Mayumi Kondo, Mitsuaki Okodo, Takeshi Tsugawa, Akihide Ryo and Hirokazu Kimura

Viruses 2022, 14(12), 2616; https://doi.org/10.3390/v14122616 - 24 Nov 2022

Cited by 13 | Viewed by 2766

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

► Show Figures

Figure 1

10 pages, 278 KiB

Open AccessReview

Effects of COVID-19 and Social Distancing on Rhinovirus Infections and Asthma Exacerbations

by Jordan E. Kreger and Marc B. Hershenson

Viruses 2022, 14(11), 2340; https://doi.org/10.3390/v14112340 - 25 Oct 2022

Cited by 12 | Viewed by 2369

Abstract

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the “common cold” and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for [...] Read more.

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the “common cold” and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae. Full article

(This article belongs to the Special Issue Rhinovirus Infections 2.0)

Journal Menu

Journal Browser

Rhinovirus Infections 2.0

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI