Rhinovirus Infections: Rethinking the Impact on Human Health and Disease

Cover
Rhinovirus Infections
Copyright
List of Contributors
Foreword
1 Rhinovirus structure, replication, and classification
	1.1 Introduction
	1.2 Biology of human rhinoviruses
		1.2.1 Rhinovirus genome organization
		1.2.2 Rhinovirus structural organization
		1.2.3 Rhinovirus replication cycle
			1.2.3.1 Binding and entry
			1.2.3.2 Uncoating
			1.2.3.3 Translation of the polyprotein and replication
			1.2.3.4 Assembly and release of infectious viral particles
	1.3 Classification of human rhinoviruses
		1.3.1 Early methods of classification
			1.3.1.1 Serotyping
			1.3.1.2 Additional characterizations of rhinoviruses
		1.3.2 Current rhinovirus classification
			1.3.2.1 Technical improvements, rhinovirus C discovery, and new classification proposals
			1.3.2.2 Genotyping
		1.3.3 Challenges in rhinovirus classification and diversity
	1.4 Summary
	References
2 Rhinovirus diversity and virulence factors
	2.1 Introduction
	2.2 Species and subtypes in clinical presentation
		2.2.1 Species and illness severity
			2.2.1.1 Association of rhinovirus species C with severe illnesses and asthma
			2.2.1.2 More than just diversity in the species
		2.2.2 Toward the identification of more pathogenic subtypes
			2.2.2.1 Cases of rhinovirus subtypes with increased pathogenicity
			2.2.2.2 An increased need for surveillance to identify circulating subtypes
	2.3 Factors contributing to increased subtype pathogenicity
		2.3.1 Rhinovirus diversity, receptor and cell tropism
		2.3.2 Viral load as an marker of illness severity
		2.3.3 Rhinovirus diversity and immune response
		2.3.4 Host cell shutdown and disease
	2.4 Rhinovirus proteases and subtype-specific disease
		2.4.1 The proteases and proteolytic roles in viral replication
			2.4.1.1 2A protease
			2.4.1.2 3C/3CD protease
	2.5 Variances in proteases between rhinovirus subtypes
	2.6 Rhinovirus proteases as virulence factors
		2.6.1 Host cell shutoff
			2.6.1.1 Nuclear pore cleavage
			2.6.1.2 Translation inhibition
			2.6.1.3 Modulation of apoptosis
	2.7 Conclusion
	References
3 Ground zero—the airway epithelium
	3.1 Introduction
	3.2 Structure of the airway epithelium
		3.2.1 Basal cells
		3.2.2 Club cells
		3.2.3 Ciliated cells
		3.2.4 Goblet cells
		3.2.5 Pulmonary neuroendocrine cells
		3.2.6 Tuft cells
		3.2.7 Pulmonary ionocytes
		3.2.8 Airway basement membrane and submucosal glands
	3.3 Functions of the airway epithelium
		3.3.1 The airway mucus barrier
		3.3.2 Barrier function of the airway epithelium
		3.3.3 Reparative function of the airway epithelium
	3.4 Rhinovirus targeting of airway epithelial cells
		3.4.1 Viral attachment
			3.4.1.1 Intercellular adhesion molecule 1 (ICAM-1)
			3.4.1.2 Low-density lipoprotein receptor (LDLR)
			3.4.1.3 Cadherin-related family member 3 (CDHR3)
			3.4.1.4 Serotype variance
	3.5 Airway epithelial cell responses to rhinovirus infection
		3.5.1 Innate immune response induction
		3.5.2 Treatment strategies to combat rhinovirus infection
	3.6 Conclusion
	References
4 Immunity to rhinoviruses
	4.1 Introduction
	4.2 Innate immune response
		4.2.1 Dendritic cells
		4.2.2 Macrophages
		4.2.3 Neutrophils
		4.2.4 Eosinophils
		4.2.5 Basophils and mast cells
		4.2.6 Natural killer cells
		4.2.7 Innate lymphoid cells
	4.3 Adaptive immune response
		4.3.1 Type I and type II immunity
		4.3.2 Type III immune response
		4.3.3 Regulatory T cells
		4.3.4 Memory T cells
		4.3.5 Neutralizing antibodies
	4.4 Conclusion
	Funding source
	References
5 Rhinoviruses and the onset of asthma
	5.1 Introduction
	5.2 Rhinovirus infections in early life
	5.3 The association between rhinovirus infections in early life and asthma
	5.4 Viral factors
	5.5 Host factors
	5.6 Environmental factors
	5.7 How could viral wheezing illnesses in early life promote asthma?
	5.8 Therapeutic implications and conclusion
	Conflicts of interest disclosure
	References
6 Exacerbations of chronic respiratory diseases
	6.1 Introduction
	6.2 Exacerbations of asthma
	6.3 Exacerbations of chronic obstructive pulmonary disease
	6.4 Exacerbations of cystic fibrosis
	6.5 Exacerbations of interstitial lung disease
	6.6 Characteristics of rhinovirus that may promote exacerbations of chronic respiratory diseases
	6.7 Rhinovirus–treatment interactions in chronic respiratory diseases
	6.8 Future directions for therapeutic approaches
	6.9 Summary
	References
7 The interplay of the host, virus, and the environment
	7.1 Introduction
	7.2 Severe infection with rhinovirus
	7.3 Allergic airway inflammation and rhinovirus infection
		7.3.1 Abnormal antiviral signaling in the airways of those with allergic asthma
	7.4 Evidence of impaired systemic immune responses to virus infection with allergic airways disease
	7.5 Virus infection worsens type 2 airway inflammation
	7.6 Chronic inflammatory airways diseases not associated with allergic and type 2 inflammation are also susceptible to rhin...
	7.7 Chronic obstructive pulmonary disease and susceptibility to rhinovirus infection
	7.8 Cellular oxidative stress and increased susceptibility to rhinovirus infection
	7.9 Conclusions
	References
8 In vivo experimental models of infection and disease
	8.1 Human models of rhinovirus infection
	8.2 Rationale for human infection studies
	8.3 Rhinovirus infection and exacerbations of asthma and chronic obstructive pulmonary disease
	8.4 Experimental rhinovirus infection in asthma
	8.5 Experimental rhinovirus infection in chronic obstructive pulmonary disease
	8.6 Future directions for human infection models
		8.6.1 Animal models of rhinovirus infection
	8.7 Mouse models
	8.8 Origins of rhinovirus mouse models
	8.9 Technical details and main findings from mouse rhinovirus infection models
	8.10 Preclinical testing in mouse models of rhinovirus infection
	8.11 Rhinovirus-induced disease exacerbation models in mice
		8.11.1 Mouse asthma exacerbation models
		8.11.2 Mouse chronic obstructive pulmonary disease exacerbation models
		8.11.3 Mouse chronic sinusitis exacerbation models
	8.12 Other rhinovirus animal models
		8.12.1 Cotton rat
	8.13 Nonhuman primates
	8.14 Animal models using other viruses
		8.14.1 Considerations, cautions, and limitations of animal infection models
		8.14.2 Future directions for animal models
	8.15 Conclusion
	References
9 Emerging therapeutic approaches
	9.1 Chemotherapeutics
		9.1.1 Viral targets
			9.1.1.1 Entry inhibitors
			9.1.1.2 Protease inhibitors
			9.1.1.3 Polymerase inhibitors
		9.1.2 Host targets
			9.1.2.1 Entry inhibitors
			9.1.2.2 The replication complex
			9.1.2.3 Novel membrane targets
			9.1.2.4 Assembly inhibitors
	9.2 Biotherapeutics and immunotherapies
		9.2.1 Innate immune stimulators
		9.2.2 Targeting virus induced pathogenic responses
		9.2.3 The use of heat against the cold
	9.3 The potential for a successful human rhinovirus vaccine
		9.3.1 The first attempts at rhinovirus vaccines: human clinical trials
		9.3.2 Second attempts at rhinovirus vaccines: animal studies
		9.3.3 Recent approaches: application of mouse and rat models of human rhinovirus infection
		9.3.4 Revisiting the multivalent inactivated rhinovirus approach
	References
10 Techniques for detection and research
	10.1 Overview
	10.2 Narrative description
		10.2.1 Does polymerase chain reaction detect replication competent virus or fragments of viral RNA not directly associated ...
		10.2.2 Should you always carry out an assay which demonstrates virus infectivity?
		10.2.3 Can polymerase chain reaction lead to false positive results?
		10.2.4 Practical ways to detect rhinovirus
		10.2.5 How to take samples: overview
		10.2.6 Sampling site
		10.2.7 Sample preparation/storage
		10.2.8 The ideal study
	10.3 Technical considerations to detecting rhinovirus
		10.3.1 Polymerase chain reaction
		10.3.2 Extraction methods
		10.3.3 Reverse transcription
		10.3.4 Primer design
		10.3.5 Polymerase chain reaction sensitivity
		10.3.6 Digital polymerase chain reaction
		10.3.7 Molecular assays to detect different rhinovirus genotypes
		10.3.8 Standard sequencing to determine rhinovirus genotype
		10.3.9 Alternative approaches to polymerase chain reaction sequencing
		10.3.10 Future perspectives
	References
Index
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