{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:11:37Z","timestamp":1785247897711,"version":"3.55.0"},"reference-count":63,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health (OER)","doi-asserted-by":"publisher","award":["R01 HL134369"],"award-info":[{"award-number":["R01 HL134369"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:p>Asthma exacerbations are often caused by rhinovirus (RV). We and others have shown that Toll-like receptor 2 (TLR2), a membrane surface receptor that recognizes bacterial lipopeptides and lipoteichoic acid, is required and sufficient for RV-induced proinflammatory responses in vitro and in vivo. We hypothesized that viral protein-4 (VP4), an internal capsid protein that is myristoylated upon viral replication and externalized upon viral binding, is a ligand for TLR2. Recombinant VP4 and myristoylated VP4 (MyrVP4) were purified by Ni-affinity chromatography. MyrVP4 was also purified from RV-A1B-infected HeLa cells by urea solubilization and anti-VP4 affinity chromatography. Finally, synthetic MyrVP4 was produced by chemical peptide synthesis. MyrVP4-TLR2 interactions were assessed by confocal fluorescence microscopy, fluorescence resonance energy transfer (FRET), and monitoring VP4-induced cytokine mRNA expression in the presence of anti-TLR2 and anti-VP4. MyrVP4 and TLR2 colocalized in TLR2-expressing HEK-293 cells, mouse bone marrow-derived macrophages, human bronchoalveolar macrophages, and human airway epithelial cells. Colocalization was absent in TLR2-null HEK-293 cells and blocked by anti-TLR2 and anti-VP4. Cy3-labeled MyrVP4 and Cy5-labeled anti-TLR2 showed an average fractional FRET efficiency of 0.24\u2009\u00b1\u20090.05, and Cy5-labeled anti-TLR2 increased and unlabeled MyrVP4 decreased FRET efficiency. MyrVP4-induced chemokine mRNA expression was higher than that elicited by VP4 alone and was attenuated by anti-TLR2 and anti-VP4. Cytokine expression was similarly increased by MyrVP4 purified from RV-infected HeLa cells and synthetic MyrVP4. We conclude that, during RV infection, MyrVP4 and TLR2 interact to generate a proinflammatory response.<\/jats:p>","DOI":"10.1152\/ajplung.00365.2018","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T21:55:48Z","timestamp":1553550948000},"page":"L57-L70","source":"Crossref","is-referenced-by-count":15,"title":["Myristoylated rhinovirus VP4 protein activates TLR2-dependent proinflammatory gene expression"],"prefix":"10.1152","volume":"317","author":[{"given":"J. Kelley","family":"Bentley","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Han","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj","family":"Jaipalli","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna L.","family":"Hinde","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lei","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charu","family":"Rajput","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Hershenson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan"},{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02309-06"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.04.020"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421178112"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1969.tb00707.x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.12.7745-7755.2005"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.05029.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.08.032"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/327482a0"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.10.050"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01070-07"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00462.2010"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.12.374"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/v9040068"},{"key":"B14","doi-asserted-by":"crossref","first-page":"621","DOI":"10.4049\/jimmunol.156.2.621","volume":"156","author":"Gern JE","year":"1996","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90688-0"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.9.5211"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.01.037"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.5.1839"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.04.020"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022194"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D029546"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.008"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002838"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0404OC"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1189"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nm1770"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.10.036"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0606412"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09641-1"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016184107"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.6774"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425336"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1021\/bi992132e"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747052"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20762"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.09.011"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1086\/339339"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000286"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900298"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502449200"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200708-1243OC"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.593426"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004294"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2004.04.002"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-346"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1208"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0354OC"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200911-1673OC"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00182.2012"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420773"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401605"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.6.L1115"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4161\/viru.2.1.13807"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602794200"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/186093"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400466200"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113003"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7401"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot4646"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002070"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901386"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5080"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0713413"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00365.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T21:33:10Z","timestamp":1694727190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00365.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,7,1]]}},"alternative-id":["10.1152\/ajplung.00365.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00365.2018","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,1]]}}}