{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:35:38Z","timestamp":1768001738160,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The temporal in vivo response of epithelial cells to a viral challenge and its association with viral clearance and clinical outcomes has been largely unexplored in asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine gene expression profiles over time in nasal epithelial cells (NECs) challenged in vivo with rhinovirus\u201016 (RV16) and compare to nasal symptoms and viral clearance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with stable mild to moderate asthma (n\u00a0=\u00a020) were challenged intranasally with RV16. Nasal brush samples for RNA sequencing were taken 7\u00a0days prior to infection and 3, 6 and 14\u00a0days post\u2010infection, and blood samples 4\u00a0days prior to infection and day 6 post\u2010infection. Viral load was measured in nasal lavage fluid at day 3, 6 and 14.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Top differentially (&gt;2.5\u2010fold increase) expressed gene sets in NECs post\u2010RV16 at days 3 and 6, compared with baseline, were interferon alpha and gamma response genes. Patients clearing the virus within 6\u00a0days (early resolvers) had a significantly increased interferon response at day 6, whereas those having cleared the virus by day 14 (late resolvers) had significantly increased responses at day 3, 6 and 14. Interestingly, patients not having cleared the virus by day 14 (non\u2010resolvers) had no enhanced interferon responses at any of these days. The daily Cold Symptom Scores (CSS) peaked at days 3 to 5 and correlated positively with interferon response genes at day 3 (R\u00a0=\u00a00.48), but not at other time\u2010points. Interferon response genes were also enhanced in blood at day 6 after RV16 challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Clinical Relevance<\/jats:title><jats:p>This study shows that viral load and clearance varies markedly over time in mild to moderate asthma patients exposed to a fixed RV16 dose. The host's nasal interferon response to RV16 at day 3 is associated with upper respiratory tract symptoms. The temporal interferon response in nasal epithelium associates with viral clearance in the nasal compartment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13481","type":"journal-article","created":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T14:08:55Z","timestamp":1565446135000},"page":"1587-1597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Rhinovirus\u201016 induced temporal interferon responses in nasal epithelium links with viral clearance and symptoms"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-7115","authenticated-orcid":false,"given":"Abilash","family":"Ravi","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Department of Respiratory Medicine University of Amsterdam Amsterdam The Netherlands"},{"name":"Amsterdam UMC, Department of Experimental Immunology, Amsterdam Infection &amp; Immunity Institute University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiping","family":"Chang","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"van de Pol","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Respiratory Medicine University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Yang","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios","family":"Aliprantis","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bob","family":"Thornton","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas N.","family":"Carayannopoulos","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An","family":"Bautmans","sequence":"additional","affiliation":[{"name":"Merck Sharp and Dohme, Europe Inc. Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Robberechts","sequence":"additional","affiliation":[{"name":"Merck Sharp and Dohme, Europe Inc. Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge","family":"De Lepeleire","sequence":"additional","affiliation":[{"name":"Merck Sharp and Dohme, Europe Inc. Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens M.","family":"Hohlfeld","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine Hannover Germany"},{"name":"German Center for Lung Research (DZL) Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Sterk","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Respiratory Medicine University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Krug","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine Hannover Germany"},{"name":"German Center for Lung Research (DZL) Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Lutter","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Department of Respiratory Medicine University of Amsterdam Amsterdam The Netherlands"},{"name":"Amsterdam UMC, Department of Experimental Immunology, Amsterdam Infection &amp; Immunity Institute University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of U\u2010BIOPRED Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2013-203728"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07953-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804181105"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041901"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.118"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1462"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201406-1039OC"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4332"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12269"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.12.369"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.03.033"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201807-1291OC"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.09.016"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201310-1767OC"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.05.030"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.028"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.08.051"},{"key":"e_1_2_8_19_1","first-page":"256","article-title":"Updated recommendations for safety\u2010testing of viral inocula used in volunteer experiments on rhinovirus colds","volume":"39","author":"Gwaltney JM","year":"1992","journal-title":"Prog Med Virol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1958.00260140099015"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00034805"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085802"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00195211"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02094-10"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000217"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201108-1462OC"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.07.013"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.036"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.07.051"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00141713"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(96)80077-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2004.037978"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201312-2235OC"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.13481","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13481","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.13481","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13481","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T17:34:47Z","timestamp":1693762487000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.13481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,31]]},"references-count":32,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1111\/cea.13481"],"URL":"https:\/\/doi.org\/10.1111\/cea.13481","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,31]]},"assertion":[{"value":"2019-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}