Human rhinovirus-induced ISG15 selectively modulates epithelial antiviral immunity.
Human rhinovirus (HRV) infections trigger exacerbations of lower airway diseases. HRV infects human airway epithelial cells and induces proinflammatory and antiviral molecules that regulate the response to HRV infection. Interferon (IFN)-stimulated gene of 15 kDa (ISG15) has been shown to regulate other viruses. We now show that HRV-16 infection induces both intracellular epithelial ISG15 expression and ISG15 secretion in vitro. Moreover, ISG15 protein levels increased in nasal secretions of subjects with symptomatic HRV infections. HRV-16-induced ISG15 expression is transcriptionally regulated via an IFN regulatory factor pathway. ISG15 does not directly alter HRV replication but does modulate immune signaling via the viral sensor protein RIG-I to impact production of CXCL10, which has been linked to innate immunity to viruses. Extracellular ISG15 also alters CXCL10 production. We conclude that ISG15 has a complex role in host defense against HRV infection, and that additional studies are needed to clarify the role of this molecule.
Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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RS
Zaheer
Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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S
Wiehler
Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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MH
Hudy
Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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SL
Traves
Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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JB
Pelikan
1] Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada [2] Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Department of Medicine, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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R
Leigh
Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, Departments of Physiology and Pharmacology, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
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Proud
D000328:Adult; D000368:Aged; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology; D012229:Rhinovirus / Q000276:immunology*; D013997:Time Factors; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
D016207:Cytokines; D014452:Ubiquitins; C074034:ISG15 protein, human