{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:27:02Z","timestamp":1761823622785},"reference-count":68,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The morbillivirus cell entry machinery consists of a fusion (F) protein trimer that refolds to mediate membrane fusion following receptor-induced conformational changes in its binding partner, the tetrameric attachment (H) protein. To identify molecular determinants that control F refolding, we generated F chimeras between measles virus (MeV) and canine distemper virus (CDV). We located a central pocket in the globular head domain of CDV F that regulates the stability of the metastable, prefusion conformational state of the F trimer. Most mutations introduced into this \u201cpocket'\u201d appeared to mediate a destabilizing effect, a phenotype associated with enhanced membrane fusion activity. Strikingly, under specific triggering conditions (i.e., variation of receptor type and H protein origin), some F mutants also exhibited resistance to a potent morbillivirus entry inhibitor, which is known to block F triggering by enhancing the stability of prefusion F trimers. Our data reveal that the molecular nature of the F stimulus and the intrinsic stability of metastable prefusion F both regulate the efficiency of F refolding and escape from small-molecule refolding blockers.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            With the aim to better characterize the thermodynamic basis of morbillivirus membrane fusion for cell entry and spread, we report here that the activation energy barrier of prefusion F trimers together with the molecular nature of the triggering \u201cstimulus\u201d (attachment protein and receptor types) define a \u201ctriggering range,\u201d which governs the initiation of the membrane fusion process. A central \u201cpocket\u201d microdomain in the globular F head contributes substantially to the regulation of the conformational stability of the prefusion complexes. The triggering range also defines the mechanism of viral escape from entry inhibitors and describes how the cellular environment can affect membrane fusion efficiency.\n          <\/jats:p>","DOI":"10.1128\/jvi.03123-13","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T02:23:50Z","timestamp":1388111030000},"page":"2951-2966","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Molecular Determinants Defining the Triggering Range of Prefusion F Complexes of Canine Distemper Virus"],"prefix":"10.1128","volume":"88","author":[{"given":"Mislay","family":"Avila","sequence":"first","affiliation":[{"name":"Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}]},{"given":"Lisa","family":"Alves","sequence":"additional","affiliation":[{"name":"Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}]},{"given":"Mojtaba","family":"Khosravi","sequence":"additional","affiliation":[{"name":"Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}]},{"given":"Nadine","family":"Ader-Ebert","sequence":"additional","affiliation":[{"name":"Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}]},{"given":"Francesco","family":"Origgi","sequence":"additional","affiliation":[{"name":"Centre for Fish and Wildlife Health (FIWI), Vetsuisse Faculty, University of Bern, Bern, Switzerland"}]},{"given":"J\u00fcrgen","family":"Schneider-Schaulies","sequence":"additional","affiliation":[{"name":"Institute for Virology and Immunobiology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}]},{"given":"Andreas","family":"Zurbriggen","sequence":"additional","affiliation":[{"name":"Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland"}]},{"given":"Richard K.","family":"Plemper","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Georgia State University, Atlanta, Georgia, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA"}]},{"given":"Philippe","family":"Plattet","sequence":"additional","affiliation":[{"name":"Division of Neurological Sciences, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir115"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02419-12"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/379441a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/348021a0"},{"key":"e_1_3_2_6_2","first-page":"1449","volume-title":"Fields virology","author":"Lamb RA","year":"2007","unstructured":"LambRAParksGD. 2007. 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