@article{37415ea37a31433193bc1a898ef6e3d7,
title = "Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1",
abstract = "Lloviu virus (LLOV), a phylogenetically divergent filovirus, is the proposed etiologic agent of die-offs of Schreibers[U+05F3]s long-fingered bats (. Miniopterus schreibersii) in western Europe. Studies of LLOV remain limited because the infectious agent has not yet been isolated. Here, we generated a recombinant vesicular stomatitis virus expressing the LLOV spike glycoprotein (GP) and used it to show that LLOV GP resembles other filovirus GP proteins in structure and function. LLOV GP must be cleaved by endosomal cysteine proteases during entry, but is much more protease-sensitive than EBOV GP. The EBOV/MARV receptor, Niemann-Pick C1 (NPC1), is also required for LLOV entry, and its second luminal domain is recognized with high affinity by a cleaved form of LLOV GP, suggesting that receptor binding would not impose a barrier to LLOV infection of humans and non-human primates. The use of NPC1 as an intracellular entry receptor may be a universal property of filoviruses.",
keywords = "Cuevavirus, Ebola, Endosomal cysteine proteases, Filoviridae, Filovirus, Lloviu virus, NPC1, Niemann-Pick C1, Viral entry, Viral glycoprotein, Viral membrane fusion, Viral receptor",
author = "Melinda Ng and Esther Ndungo and Jangra, {Rohit K.} and Yingyun Cai and Elena Postnikova and Radoshitzky, {Sheli R.} and Dye, {John M.} and {Ram{\'i}rez de Arellano}, Eva and Ana Negredo and Gustavo Palacios and Kuhn, {Jens H.} and Kartik Chandran",
note = "Funding Information: We thank Rohini G. Sandesara and Tyler Krause for excellent technical support, and Jiro Wada (Integrated Research Facility at Fort Detrick) for help with creating supplementary figures. We also thank Margaret C. Kielian (Einstein) and Dan S. Ory (Washington University School of Medicine) for their gift of the FD11 and M12 cell lines, respectively. This work was supported by the Albert Einstein College of Medicine and by NIH Grant R01 AI088027 (to K.C.). K.C. and R.K.J. were additionally supported by a fellowship from the Irma T. Hirschl/Monique Weill-Caulier Trust (to K.C.). J.M.D. was supported by JSTO-CBD Defense Threat Reduction Agency project CB3947 . A.N. was supported by a RICET Network on Tropical Diseases-ISCIII. E.R.A. was supported by a Sara Borrel program FIS-Spain. G.P. was supported by Defense Threat Reduction Agency Project 1881290 . The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense, or the US Department of Health and Human Services, or of the institutions and companies affiliated with the authors. YC, EP, and JHK performed this work as employees of Tunnell Government Services, Inc., a subcontractor to Battelle Memorial Institute, under Battelle׳s prime contract with NIAID , under Contract no. HHSN272200700016I . Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
month = nov,
day = "1",
doi = "10.1016/j.virol.2014.08.019",
language = "English (US)",
volume = "468",
pages = "637--646",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
}
