{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:41:51Z","timestamp":1791510111138,"version":"4.3.4"},"reference-count":115,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-159635"],"award-info":[{"award-number":["PJT-159635"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science and Engineering Research Council of Canada","award":["RGPIN-2018-03861"],"award-info":[{"award-number":["RGPIN-2018-03861"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v12111328","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T06:23:52Z","timestamp":1605767032000},"page":"1328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Rhinovirus-Induced Modulation of Epithelial Phenotype: Role in Asthma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7333-2610","authenticated-orcid":false,"given":"Aubrey N.","family":"Michi","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Love","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9629-6595","authenticated-orcid":false,"given":"David","family":"Proud","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Asthma (2012). Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma. GINA Reports."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1398-9995.2004.00526.x","article-title":"The global burden of asthma: Executive summary of the GINA dissemination committee report","volume":"59","author":"Masoli","year":"2004","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1378\/chest.15-1335","article-title":"Rhinovirus in the pathogenesis and clinical course of asthma","volume":"148","author":"Jamieson","year":"2015","journal-title":"Chest"},{"key":"ref_4","first-page":"201","article-title":"Role of rhinovirus infections in asthma","volume":"29","author":"Proud","year":"2011","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1067\/mai.2003.33","article-title":"Rhinovirus-induced wheezing in infancy-the first sign of childhood asthma?","volume":"111","author":"Reijonen","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1164\/rccm.200802-309OC","article-title":"Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children","volume":"178","author":"Jackson","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1093\/infdis\/171.5.1329","article-title":"Localization of human rhinovirus replication in the upper respiratory tract by in situ hybridization","volume":"171","author":"Arruda","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1086\/315513","article-title":"Rhinoviruses infect the lower airways","volume":"181","author":"Papadopoulos","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1086\/339339","article-title":"Similar frequency of rhinovirus-infectable cells in upper and lower airway epithelium","volume":"185","author":"Mosser","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1165\/rcmb.2009-0244OC","article-title":"Interleukin-13 induced mucous metaplasia increases susceptibility of human airway epithelium to rhinovirus infection","volume":"43","author":"Boushey","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1165\/rcmb.2013-0395OC","article-title":"Th2-type cytokine-induced mucus metaplasia decreases susceptibility of human bronchial epithelium to rhinovirus infection","volume":"51","author":"Jakiela","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12931-017-0567-0","article-title":"Rhinovirus c targets ciliated airway epithelial cells","volume":"18","author":"Griggs","year":"2017","journal-title":"Respir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12931-019-1120-0","article-title":"Rhinovirus replication and innate immunity in highly differentiated human airway epithelial cells","volume":"20","author":"Warner","year":"2019","journal-title":"Respir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1513\/pats.201006-039RN","article-title":"Rhinovirus infections in the upper airway","volume":"8","author":"Winther","year":"2011","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1172\/JCI118067","article-title":"Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure","volume":"96","author":"Subauste","year":"1995","journal-title":"J. Clin. Invest."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3109\/00016488409130994","article-title":"Light and scanning electron microscopy of nasal biopsy material from patients with naturally acquired common colds","volume":"97","author":"Winther","year":"1984","journal-title":"Acta. Otolaryngol. (Stockh)"},{"key":"ref_17","first-page":"L749","article-title":"Rhinovirus infection of primary cultures of human tracheal epithelium: Role of ICAM-1 and IL-1\u03b2","volume":"273","author":"Terajima","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.4049\/jimmunol.172.7.4637","article-title":"Human rhinovirus infection induces airway epithelial cell production of human \u03b2-defensin-2 both in vitro and in vivo","volume":"172","author":"Proud","year":"2004","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"L85","DOI":"10.1152\/ajplung.00397.2004","article-title":"Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection","volume":"289","author":"Spurrell","year":"2005","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.jaci.2008.01.067","article-title":"Human rhinovirus infection enhances airway epithelial cell production of growth factors involved in airway remodeling","volume":"121","author":"Leigh","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/mi.2013.128","article-title":"Human rhinovirus-induced ISG15 selectively modulates epithelial antiviral immunity","volume":"7","author":"Zaheer","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1093\/infdis\/169.5.1007","article-title":"Increased levels of interleukin-1 are detected in nasal secretions of volunteers during experimental rhinovirus colds","volume":"169","author":"Proud","year":"1994","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1111\/cea.12309","article-title":"Epithelial function and dysfunction in asthma","volume":"44","author":"Loxham","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1183\/16000617.0101-2015","article-title":"Bronchial epithelium in children: A key player in asthma","volume":"25","author":"Carsin","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.jaci.2007.10.025","article-title":"Epithelium dysfunction in asthma","volume":"120","author":"Holgate","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.jaci.2011.05.038","article-title":"Defective epithelial barrier function in asthma","volume":"128","author":"Xiao","year":"2011","journal-title":"J Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1136\/thx.47.7.499","article-title":"The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects","volume":"47","author":"Montefort","year":"1992","journal-title":"Thorax"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Singhania, A., Rupani, H., Jayasekera, N., Lumb, S., Hales, P., Gozzard, N., Davies, D.E., Woelk, C.H., and Howarth, P.H. (2017). Altered epithelial gene expression in peripheral airways of severe asthma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0168680"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1164\/rccm.200603-392OC","article-title":"Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma","volume":"174","author":"Kicic","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1165\/rcmb.2011-0031OC","article-title":"Intrinsic phenotypic differences of asthmatic epithelium and its inflammatory responses to respiratory syncytial virus and air pollution","volume":"45","author":"Hackett","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jaci.2011.11.035","article-title":"Airway epithelial cells from asthmatic children differentially express proremodeling factors","volume":"129","author":"Powers","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.jaci.2014.04.007","article-title":"Asthmatic airway epithelial cells differentially regulate fibroblast expression of extracellular matrix components","volume":"134","author":"Reeves","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1164\/rccm.200801-136OC","article-title":"Rhinovirus disrupts the barrier function of polarized airway epithelial cells","volume":"178","author":"Sajjan","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0091-6749(00)90066-6","article-title":"Epithelial-mesenchymal interactions in the pathogenesis of asthma","volume":"105","author":"Holgate","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-065X.2011.01030.x","article-title":"The sentinal role of the airway epithelium in asthma pathogenesis","volume":"242","author":"Holgate","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6859","DOI":"10.4049\/jimmunol.177.10.6859","article-title":"Syk is downstream of intercellular adhesion molecule-1 and mediates human rhinovirus activation of p38 MAPK in airway epithelial cells","volume":"177","author":"Wang","year":"2006","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"870","DOI":"10.4049\/jimmunol.180.2.870","article-title":"Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization","volume":"180","author":"Lau","year":"2008","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1128\/JVI.02309-06","article-title":"Rhinovirus activates interleukin-8 expression via a Src\/p110\u03b2 phosphatylinositol 3-kinase pathway in human airway epithelial cells","volume":"81","author":"Bentley","year":"2007","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1096\/fj.06-5806fje","article-title":"H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression","volume":"20","author":"Sajjan","year":"2006","journal-title":"FASEB J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4049\/jimmunol.1800547","article-title":"Rhinovirus and bacteria synergistically induce IL-17C release from human airway epithelial cells to promote neutrophil recruitment","volume":"202","author":"Jamieson","year":"2019","journal-title":"J. Immunol."},{"key":"ref_41","first-page":"121","article-title":"CXCL10\/IP10 in infectious diseases pathogenesis and potential therapeutic implications","volume":"22","author":"Liu","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4049\/jimmunol.156.1.322","article-title":"Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release","volume":"156","author":"Loetscher","year":"1996","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/347669a0","article-title":"Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES","volume":"347","author":"Schall","year":"1990","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1084\/jem.176.6.1489","article-title":"RANTES and macrophage inflammatory protein 1\u03b1 induce the migration and activation of normal human eosinophil granulocytes","volume":"176","author":"Rot","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1165\/ajrcmb.20.6.3261","article-title":"Rhinovirus replication causes RANTES production in primary bronchial epithelial cells","volume":"20","author":"Schroth","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Slater, L., Bartlett, N.W., Haas, J.J., Zhu, J., Message, S.D., Walton, R.P., Sykes, A., Dahdaleh, S., Clarke, D.L., and Belvisi, M.G. (2010). Co-ordinated role of TLR-3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001178"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1165\/rcmb.2013-0129OC","article-title":"Transcriptional and epigenetic modulation of human rhinovirus-induced CXCL10 production by cigarette smoke","volume":"50","author":"Hudy","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.jaci.2017.06.027","article-title":"Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: A randomized controlled study","volume":"141","author":"Silkoff","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/viru.2.1.13807","article-title":"Human rhinovirus recognition in non-immune cells is mediated by Toll-like receptors and MDA-5, which trigger a synergetic pro-inflammatory immune response","volume":"2","author":"Triantafilou","year":"2011","journal-title":"Virulence"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.4049\/jimmunol.1502702","article-title":"TLR2 activation limits rhinovirus-srimulated CXCL-10 by attenuating IRAK-1-dependent IL-33 receptor signaling in human bronchial epithelial cells","volume":"197","author":"Ganesan","year":"2016","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1165\/rcmb.2013-0032OC","article-title":"Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchiall cells","volume":"49","author":"Triantafilou","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1128\/JVI.03039-13","article-title":"Nod-like receptor X-1 is required for rhinovirus-induced barrier dysfunction in airway epithelial cells","volume":"88","author":"Unger","year":"2014","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1165\/rcmb.2009-0203OC","article-title":"Human rhinovirus-induced epithelial production of CXCL10 is dependent upon IFN Regulatory Factor-1","volume":"43","author":"Zaheer","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bosco, A., Wiehler, S., and Proud, D. (2016). Interferon regulatory factor 7 regulates airway epithelial cell responses to human rhinovirus infection. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2405-z"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.4049\/jimmunol.0802401","article-title":"Selective transcriptional down-regulation of human rhinovirus-induced production of CXCL10 from airway epithelial cells via the MEK1 pathway","volume":"182","author":"Zaheer","year":"2009","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1086\/513922","article-title":"Association between interleukin-8 concentration in nasal secretions and severity of symptoms of experimental rhinovirus colds","volume":"26","author":"Turner","year":"1998","journal-title":"Cli. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1086\/314618","article-title":"RANTES, macrophage-inhibitory protein 1\u03b1, and the eosinophil product major basic protein are released into upper respiratory secretions during virus-induced asthma exacerbations in children","volume":"179","author":"Teran","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1164\/ajrccm.155.4.9105080","article-title":"Role of nasal interleukin-8 in neutrophil recruitment and activation in children with virus-induced asthma","volume":"155","author":"Teran","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1164\/ajrccm.161.4.9812061","article-title":"Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma. Clinical and biologic significance","volume":"161","author":"Shaugnessy","year":"2000","journal-title":"Am. J. Respir Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1164\/rccm.200805-670OC","article-title":"Gene expression profiles during in vivo human rhinovirus infection: Insights into the host response","volume":"178","author":"Proud","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Proud, D., Hudy, M.H., Wiehler, S., Zaheer, R.S., Amin, M.A., Pelikan, J.B., Tacon, C.E., Tonsaker, T.O., Walker, B.L., and Kooi, C. (2012). Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040762"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1067\/mai.2001.112028","article-title":"Rhinovirus infection induces expression of type 2 nitric oxide synthase in human respiratory epithelial cells in vitro and in vivo","volume":"107","author":"Sanders","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1128\/JVI.72.2.934-942.1998","article-title":"Nitric oxide inhibits rhinovirus-induced cytokine production and viral replication in a human respiratory epithelial cell line","volume":"72","author":"Sanders","year":"1998","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jaci.2008.09.041","article-title":"Nitric oxide inhibits human rhinovirus-induced transcriptional activation of CXCL10 in airway epithelial cells","volume":"123","author":"Koetzler","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jaci.2004.01.755","article-title":"Role of nasal nitric oxide in the resolution of experimental rhinovirus infection","volume":"113","author":"Sanders","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1136\/thoraxjnl-2012-202909","article-title":"Rhinovirus-induced interferon production is not deficient in well controlled asthma","volume":"69","author":"Sykes","year":"2013","journal-title":"Thorax"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1084\/jem.20041901","article-title":"Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus","volume":"201","author":"Wark","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nm1462","article-title":"Role of deficient type-III interferon-\u03bb production in asthma exacerbations","volume":"12","author":"Contoli","year":"2006","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/mi.2012.118","article-title":"Impaired innate interferon induction in severe therapy resistant atopic asthmatic children","volume":"6","author":"Edwards","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.jaci.2009.03.010","article-title":"In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects","volume":"123","author":"Favoreto","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/mi.2009.109","article-title":"Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma","volume":"3","author":"Bochkov","year":"2010","journal-title":"Mucosal. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1164\/rccm.201310-1767OC","article-title":"Comparison of viral load in individuals with and without asthma during infections with rhinovirus","volume":"189","author":"Kennedy","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1164\/rccm.201312-2235OC","article-title":"The effect of inhaled IFN-\u03b2 on worsening of asthma symptoms caused by viral infections. A randomized trial","volume":"190","author":"Djukanovic","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7067","DOI":"10.1128\/JVI.75.15.7067-7077.2001","article-title":"Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10\/IP-10 gene expression by astrocytes in vivo and in vitro","volume":"75","author":"Asensio","year":"2001","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"42013","DOI":"10.1074\/jbc.M110.165936","article-title":"Transcription factor redundancy ensures induction of the antiviral state","volume":"285","author":"Schmid","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ashley, C.L., Abendroth, A., McSharry, B.P., and Slobedman, B. (2019). Interferon-independent upregulation of interferon-stimulated genes during human cytolegalovirus infection is dependent upon IRF3 expression. Viruses, 11.","DOI":"10.3390\/v11030246"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1513\/pats.200402-009MS","article-title":"Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease","volume":"1","author":"Jeffery","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1164\/rccm.200702-212OC","article-title":"Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers","volume":"176","author":"Saglani","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.jaci.2012.08.044","article-title":"Increased airway smooth muscle in preschool wheezers who have asthma at school age","volume":"131","author":"Ullmann","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1183\/09031936.00161907","article-title":"Serial viral infections in infants with recurrent respiratory illnesses","volume":"32","author":"Jartti","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1164\/rccm.201104-0660OC","article-title":"Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life","volume":"185","author":"Jackson","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1440-1843.2010.01918.x","article-title":"Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo","volume":"16","author":"Kuo","year":"2011","journal-title":"Respirology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1165\/rcmb.2019-0004OC","article-title":"Rhinovirus C15 induces airway hyperresponsiveness via calcium mobilization in airway smooth muscle","volume":"62","author":"Parikh","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1165\/rcmb.2009-0216OC","article-title":"Human rhinovirus infection of airway epithelial cells upregulates MMP-9 production via NF-\u03baB","volume":"43","author":"Tacon","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jaci.2005.11.005","article-title":"Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinovirus","volume":"117","author":"Psarras","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2015.12.1308","article-title":"Chemokine release from human rhinovirus-infected airway epithelial cells promotes fibroblast migration","volume":"138","author":"Shelfoon","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1165\/rcmb.2016-0252OC","article-title":"Human rhinovirus infection of epithelial cells modulates airway smooth muscle migration","volume":"56","author":"Shariff","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1165\/rcmb.2008-0223OC","article-title":"Rhinovirus-induced major airway mucin production involves a novel TLR3-EGFR-dependent pathway","volume":"40","author":"Zhu","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1183\/09031936.00026910","article-title":"Rhinovirus induces MUC5AC in a human infection model and in vitro via NF-\u03baB and EGFR pathways","volume":"36","author":"Hewson","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bai, J., Smock, S.L., Jackson, G.R.J., MacIsaac, K.D., Huang, Y., Mankus, C., Oldach, J., Roberts, B., Ma, Y.-L., and Klappenbach, J.A. (2015). Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118286"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"C1213","DOI":"10.1152\/ajpcell.00558.2003","article-title":"The tight junction: A multifunctional complex","volume":"286","author":"Schneeberger","year":"2004","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/cea.13097","article-title":"Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma","volume":"48","author":"Looi","year":"2018","journal-title":"Clin. Exp. Allergy"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jaci.2014.01.029","article-title":"Effects of rhinovirus species on viral replication and cytokine production","volume":"134","author":"Nakagome","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6795","DOI":"10.1128\/JVI.02074-10","article-title":"Rhinovirus-induced barrier dysfunction in polarized airway epithelial cells is mediated by NADPH oxidase 1","volume":"85","author":"Comstock","year":"2011","journal-title":"J. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.4049\/jimmunol.179.2.1080","article-title":"TLR-3 and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells","volume":"179","author":"Kato","year":"2007","journal-title":"J. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"256ra134","DOI":"10.1126\/scitranslmed.3009124","article-title":"Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation","volume":"6","author":"Beale","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1164\/rccm.201406-1039OC","article-title":"IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo","volume":"190","author":"Jackson","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"L731","DOI":"10.1152\/ajplung.00362.2016","article-title":"Rhinovirus-bacteria coexposure synergistically induces CCL20 production from human bronchial epithelial cells","volume":"312","author":"Maciejewski","year":"2017","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1172\/JCI118431","article-title":"Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor \u03baB-dependent transcriptional activation","volume":"97","author":"Zhu","year":"1996","journal-title":"J. Clin. Invest."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/mi.2014.2","article-title":"IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection","volume":"7","author":"Jayaraman","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2174\/138945006776818647","article-title":"Interactions between airway epithelial cells and dendritic cells: Implications for the regulation of airway inflammation","volume":"7","author":"Upham","year":"2006","journal-title":"Curr. Drug Targets"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s11882-996-0006-7","article-title":"Thymic stromal lymphopoietin: A potential therapeutic target for allergy and asthma","volume":"6","author":"Huston","year":"2006","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1086\/315463","article-title":"Rhinovirus infection induces major histocompatability complex class I and costimulatory molecule upregulation on respiratory epithelial cells","volume":"181","author":"Papi","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1165\/rcmb.2004-0129OC","article-title":"Constitutive and inducible expression of B7 family of ligands by human airway epithelial cells","volume":"33","author":"Kim","year":"2005","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.jaci.2008.02.009","article-title":"Induction of B7-H1 and B7-DC expression on airway epithelial cells by the Toll-like receptor 3 agonist double-stranded RNA and human rhinovirus infection: In vivo and in vitro studies","volume":"121","author":"Heinecke","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.4049\/jimmunol.161.10.5138","article-title":"LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production","volume":"161","author":"Salomon","year":"1998","journal-title":"J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1600-065X.2011.01033.x","article-title":"Epithelial cells and airway diseases","volume":"242","author":"Proud","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1097\/01.inf.0000053889.39392.a7","article-title":"Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma","volume":"22","author":"Martinez","year":"2003","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jaci.2015.02.024","article-title":"Association between respiratory infections in early life and later asthma is independent of virus type","volume":"136","author":"Vissing","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1164\/rccm.201405-0901PP","article-title":"Toward primary prevention of asthma. Reviewing the evidence for early-life respiratory viral infections as modifiable risk factors to prevent childhood asthma","volume":"191","author":"Feldman","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12931-015-0185-7","article-title":"Fibroblast-myofibroblast transition is differentially regulated by bronchial epithelial cells from asthmatic children","volume":"16","author":"Reeves","year":"2015","journal-title":"Respir. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1183\/09031936.00092410","article-title":"Association between human rhinovirus C and severity of acute asthma in children","volume":"37","author":"Bizzintino","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1164\/rccm.201303-0498OC","article-title":"Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions","volume":"188","author":"Cox","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1097\/INF.0000000000002141","article-title":"Rhinovirus species in children with severe bronchiolitis: Multicenter cohort studies in the United States and Finland","volume":"38","author":"Hasagawa","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1164\/rccm.201202-0330OC","article-title":"Human rhinovirus species and season of infection determine illness severity","volume":"186","author":"Lee","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/11\/1328\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:34:11Z","timestamp":1760178851000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/11\/1328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":115,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["v12111328"],"URL":"https:\/\/doi.org\/10.3390\/v12111328","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]}}}