Special Issue "Rhinovirus Infections"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 12792

Special Issue Editor

Prof. Dr. Gary McLean
E-Mail Website1 Website2
Guest Editor
London Metropolitan University and Imperial College London, London, UK
Interests: rhinovirus; HCMV; HIV; monoclonal antibodies; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Rhinoviruses are small nonenveloped RNA viruses belonging to the family picornaviridae and are recognized as the major cause of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disorder (COPD) in humans. These viruses are extremely antigenically diverse in structure, with approximately 160 distinct serotypes/strains grouped into three types, A, B, and C, with further distinctions based on entry receptor requirements where three different cell-surface molecules have been described. Immunity to rhinoviruses is generally considered to be serotype-specific. Despite intensive studies since their discovery in the 1960s, no effective antiviral or vaccine has been invented to combat these ubiquitous pathogens. Thus, humans can expect to have three to five infections per year, and significantly more in children.

In this Special Issue of Viruses, we aim to gather research and review papers that contribute to an improved understanding of rhinovirus structure, classification, infections, epidemiology, and immunopathology, or that report the development of vaccines or antiviral agents.

Prof. Gary McLean
Guest Editor

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Keywords

  • rhinovirus
  • infections
  • immunopathology
  • vaccines
  • T cells
  • antibodies

Published Papers (12 papers)

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Research

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Article
Rhinovirus Infections among Hematopoietic Stem Cell Transplant Recipients: A Pre-Transplant Dilemma?
Viruses 2022, 14(2), 267; https://doi.org/10.3390/v14020267 - 28 Jan 2022
Cited by 1 | Viewed by 784
Abstract
Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients’ depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed [...] Read more.
Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients’ depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were transplanted between 1 January 2010 and 31 October 2019 in the Geneva University Hospitals with at least one RVI before or after transplantation. At least one RVI was detected in 319/533 (63.5%) transplanted patients. Rhinoviruses were most frequently identified (37%), followed by human coronaviruses (17.1%), parainfluenza viruses (13.9%), and influenza viruses (9.9%). First infection in the post-transplant period occurred at a mean time of 334 days (SD 338). Specific analysis of a subgroup of 65 patients with pre-transplant RVIs was performed. Among them, 39 (59%) patients had symptoms and 14 (21.2%) had a lower respiratory tract infection. Four patients (6.1%) (three rhinovirus and one influenza) needed an intensive care unit admission, of which, three (4.5%) (two rhinovirus and one influenza) were intubated. The patient with influenza infection diagnosed the day of the transplantation died within the first 30 days of the infection. Two patients with rhinovirus infection died within 3 months of unrelated causes. Our data show that rhinovirus infections are predominant in allo-HSCT patients, including among pre-transplant infections; however, mortality due to pre-transplant RVI is low and was only clearly identified in one patient with influenza infection. RVI within the month preceding allo-HSCT is not associated with direct morbidity or mortality in this cohort. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Communication
RIPK1 Is Cleaved by 3C Protease of Rhinovirus A and B Strains and Minor and Major Groups
Viruses 2021, 13(12), 2402; https://doi.org/10.3390/v13122402 - 30 Nov 2021
Cited by 1 | Viewed by 563
Abstract
Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that [...] Read more.
Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that modulates various cell death and cell survival pathways. In the current study, we have investigated whether this cleavage is conserved across selected RV strains. RIPK1 was cleaved in cells infected with strains representing diversity across phylogenetic groups (A and B) and receptor usage (major and minor groups). The cleavage was abrogated in the presence of the specific 3C protease inhibitor, Rupintrivir. Interestingly, there appears to be involvement of another protease (maybe 2A protease) in RIPK1 cleavage in strains belonging to genotype B. Our data show that 3C protease from diverse RV strains cleaves RIPK1, highlighting the importance of the cleavage to the RV lifecycle. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Article
Human Rhinoviruses in Adult Patients in a Tertiary Care Hospital in Germany: Molecular Epidemiology and Clinical Significance
Viruses 2021, 13(10), 2027; https://doi.org/10.3390/v13102027 - 08 Oct 2021
Cited by 3 | Viewed by 618
Abstract
Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in adult patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and the partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from [...] Read more.
Rhinoviruses (RVs) constitute a substantial public health burden. To evaluate their abundance and genetic diversity in adult patients, RV RNA in respiratory samples was assessed using real-time RT-PCR and the partial nucleic acid sequencing of viral genomes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of adult RV infections. In total, the respiratory specimens of 284 adult patients (18–90 years), collected from 2013 to 2017, were analyzed. Infections occurred throughout the entire year, with peaks occurring in fall and winter, and showed a remarkably high intra- and interseasonal diversity of RV genotypes. RV species were detected in the following ratios: 60.9% RV-A 173, 12.7% RV-B, and 26.4% RV-C. No correlations between RV species and underlying comorbidities such as asthma (p = 0.167), COPD (p = 0.312) or immunosuppression (p = 0.824) were found. However, 21.1% of the patients had co-infections with other pathogens, which were associated with a longer hospital stay (p = 0.024), LRTI (p < 0.001), and pneumonia (p = 0.01). Taken together, this study shows a pronounced genetic diversity of RV in adults and underlines the important role of co-infections. No correlation of specific RV species with a particular clinical presentation could be deduced. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Article
Epidemiology of the Rhinovirus (RV) in African and Southeast Asian Children: A Case-Control Pneumonia Etiology Study
Viruses 2021, 13(7), 1249; https://doi.org/10.3390/v13071249 - 27 Jun 2021
Cited by 3 | Viewed by 1208
Abstract
Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1–59 months) hospitalized with [...] Read more.
Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1–59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3–1.6). This association was driven by the children aged 12–59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8–2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4–2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Article
Microarray Technology May Reveal the Contribution of Allergen Exposure and Rhinovirus Infections as Possible Triggers for Acute Wheezing Attacks in Preschool Children
Viruses 2021, 13(5), 915; https://doi.org/10.3390/v13050915 - 15 May 2021
Viewed by 1011
Abstract
Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal [...] Read more.
Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and -negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Article
Viral Loads and Disease Severity in Children with Rhinovirus-Associated Illnesses
Viruses 2021, 13(2), 295; https://doi.org/10.3390/v13020295 - 13 Feb 2021
Cited by 3 | Viewed by 933
Abstract
The role of rhinoviruses (RVs) in children with clinical syndromes not classically associated with RV infections is not well understood. We analyzed a cohort of children ≤21 years old who were PCR+ for RV at a large Pediatric Hospital from 2011 to 2013. [...] Read more.
The role of rhinoviruses (RVs) in children with clinical syndromes not classically associated with RV infections is not well understood. We analyzed a cohort of children ≤21 years old who were PCR+ for RV at a large Pediatric Hospital from 2011 to 2013. Using univariate and multivariable logistic regression, we analyzed the associations between demographic, clinical characteristics, microbiology data, and clinical outcomes in children with compatible symptoms and incidental RV detection. Of the 2473 children (inpatients and outpatients) with an RV+ PCR, 2382 (96%) had compatible symptoms, and 91 (4%) did not. The overall median age was 14 months and 78% had underlying comorbidities. No differences in RV viral loads were found according to the presence of compatible symptoms, while in children with classic RV symptoms, RV viral loads were higher in single RV infections versus RV viral co-infections. Bacterial co-infections were more common in RV incidental detection (7.6%) than in children with compatible symptoms (1.9%, p < 0.001). The presence of compatible symptoms independently increased the odds ratio (OR, 95% CI) of hospitalization 4.8 (3.1–7.4), prolonged hospital stays 1.9 (1.1–3.1), need for oxygen 12 (5.8–25.0) and pediatric intensive care unit (PICU) admission 4.13 (2.0–8.2). Thus, despite comparable RV loads, disease severity was significantly worse in children with compatible symptoms. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Article
Solution NMR Determination of the CDHR3 Rhinovirus-C Binding Domain, EC1
Viruses 2021, 13(2), 159; https://doi.org/10.3390/v13020159 - 22 Jan 2021
Cited by 1 | Viewed by 987
Abstract
Cadherin Related Family Member 3 (CDHR3) is the identified and required cellular receptor for all virus isolates in the rhinovirus-C species (RV-C). Cryo-EM determinations recently resolved the atomic structure of RV-C15a, and subsequently, a complex of this virus bound to CDHR3 extracellular domain [...] Read more.
Cadherin Related Family Member 3 (CDHR3) is the identified and required cellular receptor for all virus isolates in the rhinovirus-C species (RV-C). Cryo-EM determinations recently resolved the atomic structure of RV-C15a, and subsequently, a complex of this virus bound to CDHR3 extracellular domain 1 (EC1), the N-terminal portion of this receptor responsible for virus interactions. The EC1 binds to a hypervariable sequence footprint on the virus surface, near the 3-fold axis of icosahedral symmetry. The key contacts involve discontinuous residues from 3 viral proteins, VP1, VP2 and VP3. That single cryo-EM EC1 structure, however, could not resolve whether the virus-receptor interface was structurally adaptable to accommodate multiple virus sequences. We now report the solution NMR determination of CDHR3 EC1, showing that this protein, in fact, is mostly inflexible, particularly in the virus-binding face. The new, higher resolution dataset identifies 3 cis-Pro residues in important loop regions, where they can influence both rigidity and overall protein conformation. The data also provide clarification about the residues involved in essential calcium ion binding, and a potential CDHR3 surface groove feature that may be involved in native protein interactions with cellular partners. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Article
Can Measurements of Inflammatory Biomarkers Be Used to Spot Respiratory Viral Infections?
Viruses 2020, 12(10), 1175; https://doi.org/10.3390/v12101175 - 17 Oct 2020
Cited by 1 | Viewed by 941
Abstract
Accurate detection of human respiratory viral infections is highly topical. We investigated how strongly inflammatory biomarkers (FeNO, eosinophils, neutrophils, and cytokines in nasal lavage fluid) and lung function parameters change upon rhinovirus 16 infection, in order to explore their potential use for infection [...] Read more.
Accurate detection of human respiratory viral infections is highly topical. We investigated how strongly inflammatory biomarkers (FeNO, eosinophils, neutrophils, and cytokines in nasal lavage fluid) and lung function parameters change upon rhinovirus 16 infection, in order to explore their potential use for infection detection. To this end, within a longitudinal cohort study, healthy and mildly asthmatic volunteers were experimentally inoculated with rhinovirus 16, and time series of these parameters/biomarkers were systematically recorded and compared between the pre- and post-infection phases of the study, which lasted two months and one month, respectively. We found that the parameters’/biomarkers’ ability to discriminate between the infected and the uninfected state varied over the observation time period. Consistently over time, the concentration of cytokines, in nasal lavage fluid, showed moderate to very good discrimination performance, thereby qualifying for disease progression monitoring, whereas lung function and FeNO, while quickly and non-invasively measurable using cheap portable devices (e.g., at airports), performed poorly. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Review

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Review
Understanding Rhinovirus Circulation and Impact on Illness
Viruses 2022, 14(1), 141; https://doi.org/10.3390/v14010141 - 13 Jan 2022
Cited by 3 | Viewed by 976
Abstract
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With [...] Read more.
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With three species and 169 subtypes, RV presents the greatest diversity within the Enterovirus genus, and despite the efforts of the research community to identify clinically relevant subtypes to target therapeutic strategies, the role of species and subtype in the clinical outcomes of RV infection remains unclear. This review aims to collect and organize data relevant to RV illness in order to find patterns and links with species and/or subtype, with a specific focus on species and subtype diversity in clinical studies typing of respiratory samples. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Review
Rhinovirus and Cell Death
Viruses 2021, 13(4), 629; https://doi.org/10.3390/v13040629 - 07 Apr 2021
Cited by 1 | Viewed by 1644
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Review
Rhinovirus-Induced Modulation of Epithelial Phenotype: Role in Asthma
Viruses 2020, 12(11), 1328; https://doi.org/10.3390/v12111328 - 19 Nov 2020
Cited by 6 | Viewed by 1239
Abstract
Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how [...] Read more.
Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how HRV-induced modulation of several aspects of epithelial cell phenotype could contribute to the development of asthma or to the induction of exacerbations. Modification of epithelial proinflammatory and antiviral responses are considered, as are alterations in an epithelial barrier function and cell phenotype. The contributions of the epithelium to airway remodeling and to the potential modulation of immune responses are also considered. The potential interactions of each type of HRV-induced epithelial phenotypic changes with allergic sensitization and allergic phenotype are also considered in the context of asthma development and of acute exacerbations. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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Other

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Perspective
Mechanisms of Rhinovirus Neutralisation by Antibodies
Viruses 2021, 13(3), 360; https://doi.org/10.3390/v13030360 - 25 Feb 2021
Cited by 4 | Viewed by 872
Abstract
Antibodies are a critical immune correlate of protection for rhinoviruses, particularly those antibodies found in the secretory compartment. For nonenveloped viruses such as rhinoviruses, antibody binding to regions of the icosahedral capsid can neutralise infections by a number of different mechanisms. The purpose [...] Read more.
Antibodies are a critical immune correlate of protection for rhinoviruses, particularly those antibodies found in the secretory compartment. For nonenveloped viruses such as rhinoviruses, antibody binding to regions of the icosahedral capsid can neutralise infections by a number of different mechanisms. The purpose of this review is to address the neutralising mechanisms of antibodies to rhinoviruses that would help progress vaccine development. At least five mechanisms of antibody neutralisation have been identified which depend to some extent on the antibody binding footprints upon the capsid. The most studied mechanisms are virion aggregation, inhibition of attachment to cells, and stabilisation or destabilisation of the capsid structure. Newer mechanisms of degradation inside the cell through cytoplasmic antibody detection or outside by phagocytosis rely on what might have been previously considered as non-neutralising antibodies. We discuss these various approaches of antibody interference of rhinoviruses and offer suggestions as to how these could influence vaccine design. Full article
(This article belongs to the Special Issue Rhinovirus Infections)
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