{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:48:05Z","timestamp":1783536485290,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Viral infections are the main cause of asthma exacerbation, particularly in children. Impaired interferon induction by the airway epithelium has been linked to increased asthma exacerbation during viral infections. Several studies have suggested that epithelial cells in asthmatic mice induce low levels of type I and type III interferons, which leads to increased viral load. However, emerging evidence suggests that epithelial cells from asthmatic individuals induce delayed interferon responses. This study aimed to assess the ability of asthmatic and healthy epithelial cells to mount interferon-associated responses after exposure to viral stimuli. Variations in gene expression associated with interferon response were analyzed using datasets obtained from the Gene Expression Omnibus (GEO) database. Airway epithelial cells derived from healthy and asthmatic individuals were infected with RNA virus and then subjected to microarray or RNA sequencing. Lung tissues obtained from the animal models (mice and rats) were analyzed using RNA sequencing. Further data analysis was performed using integrated differential expression and pathway analysis (iDEP). Viral infection of airway epithelial cells derived from healthy and asthmatic subjects induces strong expression of interferon- and interferon-related genes. Interferon-stimulated genes (ISGs) were robustly induced in both asthmatic and healthy human epithelial cells after viral infection. However, the induction of virus-induced interferon-related responses was significantly lower in the lung tissues of animals with pre-allergic inflammation. Although previous studies have reported that the antiviral-interferon response is impaired or diminished in asthmatic individuals, our findings suggest that interferon-associated transcriptional responses are preserved in the airway epithelial cells of asthmatics during viral infection. This suggests that asthmatic epithelial cells induce an antiviral immune response, characterized by the induction of interferon-associated genes necessary for viral removal. Future studies should investigate the mechanisms underlying virus-induced asthma exacerbation.<\/jats:p>","DOI":"10.3390\/ijms27146113","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"6113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interferon-Associated Transcriptional Responses Are Preserved in Human Asthmatic Airway Epithelial Cells During Viral Infection"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-1489","authenticated-orcid":false,"given":"Hamad H.","family":"Alanazi","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat 77442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S2213-2600(24)00383-7","article-title":"Asthma: Epidemiology, risk factors, and opportunities for prevention and treatment","volume":"13","author":"Jayasooriya","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S0140-6736(10)61380-3","article-title":"Role of viral respiratory infections in asthma and asthma exacerbations","volume":"376","author":"Busse","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.pccm.2025.08.003","article-title":"Unraveling the mechanisms of virus-induced asthma exacerbation: Epithelial injury, immune dysregulation, and novel interventions","volume":"3","author":"Du","year":"2025","journal-title":"Chin. Med. J. Pulm. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4S","DOI":"10.1016\/S0002-9343(01)01058-0","article-title":"Epidemiology of viral respiratory infections","volume":"112","author":"Monto","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1515\/hsz-2018-0304","article-title":"The role of the innate immune system on pulmonary infections","volume":"400","author":"McLaughlin","year":"2019","journal-title":"Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"167079","DOI":"10.1016\/j.bbadis.2024.167079","article-title":"House dust mite allergens induce Ca2+ signalling and alarmin responses in asthma airway epithelial cells","volume":"1870","author":"Ouyang","year":"2024","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41423-025-01261-2","article-title":"Type 2 immunity in allergic diseases","volume":"22","author":"Ogulur","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ghezzi, M., Pozzi, E., Abbattista, L., Lonoce, L., Zuccotti, G.V., and D\u2019Auria, E. (2021). Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective. Children, 8.","DOI":"10.3390\/children8121165"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111240","DOI":"10.1016\/j.isci.2024.111240","article-title":"Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases","volume":"27","author":"She","year":"2024","journal-title":"iScience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"L1018","DOI":"10.1152\/ajplung.00065.2008","article-title":"Interleukin-1beta mediates human airway epithelial cell migration via NF-kappaB","volume":"295","author":"White","year":"2008","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.coviro.2011.10.026","article-title":"Type I interferons: Diversity of sources, production pathways and effects on immune responses","volume":"1","author":"Swiecki","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102400","DOI":"10.1016\/j.coi.2023.102400","article-title":"Differential signaling by type-I and type-III interferons in mucosa","volume":"86","author":"Stanifer","year":"2024","journal-title":"Curr. Opin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e02582-24","DOI":"10.1128\/mbio.02582-24","article-title":"Interference without interferon: Interferon-independent induction of interferon-stimulated genes and its role in cellular innate immunity","volume":"15","author":"Swaraj","year":"2024","journal-title":"mBio"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12720","DOI":"10.1128\/JVI.01471-07","article-title":"Viral Encounters with 2\u2032,5\u2032-Oligoadenylate Synthetase and RNase L during the Interferon Antiviral Response","volume":"81","author":"Silverman","year":"2007","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13524","DOI":"10.1038\/s41598-024-63314-2","article-title":"Induction and antiviral activity of ferret myxovirus resistance (Mx) protein 1 against influenza A viruses","volume":"14","author":"Farrukee","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, J., Luo, Y., Katiyar, H., Liang, C., and Liu, Q. (2024). The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies. Viruses, 16.","DOI":"10.3390\/v16050734"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kim, S.R. (2022). Viral Infection and Airway Epithelial Immunity in Asthma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179914"},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.jaci.2012.03.044","article-title":"Rhinovirus 16\u2013induced IFN-\u03b1 and IFN-\u03b2 are deficient in bronchoalveolar lavage cells in asthmatic patients","volume":"129","author":"Sykes","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sykes, A., Edwards, M.R., Macintyre, J., Del Rosario, A., Gielen, V., Haas, J., Kon, O.M., McHale, M., and Johnston, S.L. (2013). TLR3, TLR4 and TLRs7-9 Induced Interferons Are Not Impaired in Airway and Blood Cells in Well Controlled Asthma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065921"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rich, H.E., Antos, D., Melton, N.R., Alcorn, J.F., and Manni, M.L. (2020). Insights Into Type I and III Interferons in Asthma and Exacerbations. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.574027"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.jaci.2014.07.013","article-title":"Interferon response and respiratory virus control are preserved in bronchial epithelial cells in asthma","volume":"134","author":"Patel","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Veerati, P.C., Troy, N.M., Reid, A.T., Li, N.F., Nichol, K.S., Kaur, P., Maltby, S., Wark, P.A.B., Knight, D.A., and Bosco, A. (2020). Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00974"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1111\/all.14421","article-title":"Epithelial cell dysfunction, a major driver of asthma development","volume":"75","author":"Heijink","year":"2020","journal-title":"Allergy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1128\/CMR.00014-10","article-title":"The airway epithelium: Soldier in the fight against respiratory viruses","volume":"24","author":"Vareille","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.4049\/jimmunol.1900720","article-title":"Immune Sensing of Aeroallergen-Associated Double-Stranded RNA Triggers an IFN Response and Modulates Type 2 Lung Inflammation","volume":"203","author":"She","year":"2019","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, D., van der Veen, T.A., de Groot, L.E.S., de Jager, M.H., Lan, A., Baarsma, H.A., Lutter, R., van der Graaf, K., Gosens, R., and Schmidt, M. (2025). Pre-Existing Allergic Inflammation Alters Both Innate and Adaptive Immune Responses in Mice Co-Infected with Influenza Virus. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083483"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"de Jong, E., Lauzon-Joset, J.F., Leffler, J., Serralha, M., Larcombe, A.N., Christophersen, C.T., Holt, P.G., Strickland, D.H., and Bosco, A. (2021). IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus\/Allergen Coexposure and OM-85-Induced Reprogramming. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.699633"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bai, J., Smock, S.L., Jackson, G.R., 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_30","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1465-9921-15-9","article-title":"dsRNA-induced changes in gene expression profiles of primary nasal and bronchial epithelial cells from patients with asthma, rhinitis and controls","volume":"15","author":"Wagener","year":"2014","journal-title":"Respir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jaci.2018.09.016","article-title":"Interferon-induced epithelial response to rhinovirus 16 in asthma relates to inflammation and FEV1","volume":"143","author":"Ravi","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.alit.2017.10.006","article-title":"Barrier dysfunction in the nasal allergy","volume":"67","author":"Fukuoka","year":"2018","journal-title":"Allergol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.immuni.2015.07.007","article-title":"Barrier Epithelial Cells and the Control of Type 2 Immunity","volume":"43","author":"Hammad","year":"2015","journal-title":"Immunity"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"2301397","DOI":"10.1183\/13993003.01397-2023","article-title":"The airway epithelium: An orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma","volume":"63","author":"Russell","year":"2024","journal-title":"Eur. Respir. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Frey, A., Lunding, L.P., Ehlers, J.C., Weckmann, M., Zissler, U.M., and Wegmann, M. (2020). More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00761"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, B., Song, G., Sun, M., Zhang, Y., and Ren, M. (2026). Airway epithelial dysfunction in asthma pathogenesis: Epigenetic mechanisms, inflammatory crosstalk, and therapeutic opportunities. Front. Allergy, 7.","DOI":"10.3389\/falgy.2026.1839974"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jaci.2016.02.035","article-title":"Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma","volume":"139","author":"Sweerus","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4168\/aair.2018.10.1.4","article-title":"Claudin may be a Potential Biomarker for Epithelial Barrier Dysfunction in Asthma","volume":"10","author":"Jin","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ge, S.X., Son, E.W., and Yao, R. (2018). iDEP: An integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2486-6"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:32:35Z","timestamp":1783531955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":40,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146113"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146113","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]}}}