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Mechanism for active membrane fusion triggering by morbillivirus attachment protein.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Ader Nadine, Brindley Melinda, Avila Mislay, Örvell Claes, Horvat Branka, Hiltensperger Georg, Schneider-Schaulies Jürgen, Vandevelde Marc, Zurbriggen Andreas, Plemper Richard K, Plattet Philippe,
Project Molecular determinants of Morbillivirus-induced non-cytolytic cell-to-cell spread
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Original article (peer-reviewed)

Journal Journal of virology
Volume (Issue) 87(1)
Page(s) 314 - 26
Title of proceedings Journal of virology
DOI 10.1128/JVI.01826-12


The paramyxovirus entry machinery consists of two glycoproteins that tightly cooperate to achieve membrane fusion for cell entry: the tetrameric attachment protein (HN, H, or G, depending on the paramyxovirus genus) and the trimeric fusion protein (F). Here, we explore whether receptor-induced conformational changes within morbillivirus H proteins promote membrane fusion by a mechanism requiring the active destabilization of prefusion F or by the dissociation of prefusion F from intracellularly preformed glycoprotein complexes. To properly probe F conformations, we identified anti-F monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes. Through heat treatment as a surrogate for H-mediated F triggering, we demonstrate with these MAbs that the morbillivirus F trimer contains a sufficiently high inherent activation energy barrier to maintain the metastable prefusion state even in the absence of H. This notion was further validated by exploring the conformational states of destabilized F mutants and stabilized soluble F variants combined with the use of a membrane fusion inhibitor (3g). Taken together, our findings reveal that the morbillivirus H protein must lower the activation energy barrier of metastable prefusion F for fusion triggering.