Chapter 23 : Rhinovirus and Respiratory Disease

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Human rhinovirus (HRV) has long been known to infect the upper respiratory tract, i.e., nasal passages, paranasal sinuses, and pharynx. However, it has recently become clear that HRV infection also causes exacerbations of chronic respiratory diseases affecting the lower respiratory tract, i.e., the larynx, trachea, bronchi, bronchioles, and alveoli. Recent data hint at the possibility that HRV infections not only cause exacerbations of asthma but also influence the severity of the disease, and they may even be involved in its initial pathogenesis. Eosinophils and eosinophil cationic protein have been detected in the airways following experimental HRV infection, and asthma patients show more eosinophils than controls. In vitro studies have noted attachment of HRV to peripheral blood monocytes and airway macrophages, with subsequent secretion of numerous proinflammatory cytokines, chemokines, and IFNs. Cultured HeLa cells were infected with lung homogenates from HRV1B-treated mice. Together, these results strongly suggest that HRV1B causes viral RNA replication with a productive infection in wild- type mice. HRV has been detected in secretions and epithelial cells of the segmental bronchial epithelium and is associated with exacerbations of chronic respiratory diseases affecting the lower airways, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). New animal models demonstrate that HRV infection and allergen exposure have synergistic effects on bronchial inflammation and hyperreactivity. The large number of serotypes of HRV indicates that a novel strategy may be necessary for generating an effective vaccine.

Citation: Hershenson M. 2010. Rhinovirus and Respiratory Disease, p 369-381. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch23
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Image of Figure 1.
Figure 1.

Steps in infection with the major group of HRVs, including ICAM ligation, endocytosis, and RNA signaling. Parallel signaling events are shown. In addition to the well-known pathways of activation of the innate immune response, HRV 3C can directly affect AP-1, NF-κB, and cytokines ( ). ssRNA, single-stranded RNA; ISRE, IFN-stimulated response element.

Citation: Hershenson M. 2010. Rhinovirus and Respiratory Disease, p 369-381. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch23
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Image of Figure 2.
Figure 2.

Model of HRV dsRNA-induced gene expression. dsRNA may be detected by the pattern recognition receptors TLR3, MDA5, and RIG-I. dsRNA detection initiates signaling through the IKKα/IKKβ and TBK1/MKKε complexes, leading to trans-activation of NF-κB and IRF3, and perhaps STAT1. Although NF-κB and IRF3 may constitute part of the same transcriptional enhanceosome, their requirements for gene expression vary for different target genes, perhaps depending on organization of the NF-κB and IFN-stimulated response elements.

Citation: Hershenson M. 2010. Rhinovirus and Respiratory Disease, p 369-381. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch23
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Image of Figure 3.
Figure 3.

Model of HRV-induced asthma exacerbation. Endotoxin exposure and allergen sensitization and challenge induce Th1- and Th2-based immune responses, respectively. Th1 stimulation leads to classical macrophage activation. HRV stimulation of classically activated macrophages induces production of CXCR2 ligands and TNF-α, leading to increased neutrophilic airway inflammation. On the other hand, Th2 stimulation leads to IL-4-mediated alternative macrophage activation. HRV stimulation of alternatively activated macrophages induces elaboration of CCR1 to -4 ligands, including eotaxin-1, leading to increased eosinophilic inflammation.

Citation: Hershenson M. 2010. Rhinovirus and Respiratory Disease, p 369-381. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch23
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