Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1

Melinda Ng, Esther Ndungo, Rohit K. Jangra, Yingyun Cai, Elena Postnikova, Sheli R. Radoshitzky, John M. Dye, Eva Ramírez de Arellano, Ana Negredo, Gustavo Palacios, Jens H. Kuhn, Kartik Chandran

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)637-646
Number of pages10
JournalVirology
Volume468
DOIs
StatePublished - Nov 1 2014

Keywords

  • Cuevavirus
  • Ebola
  • Endosomal cysteine proteases
  • Filoviridae
  • Filovirus
  • Lloviu virus
  • NPC1
  • Niemann-Pick C1
  • Viral entry
  • Viral glycoprotein
  • Viral membrane fusion
  • Viral receptor

ASJC Scopus subject areas

  • Virology

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    Ng, M., Ndungo, E., Jangra, R. K., Cai, Y., Postnikova, E., Radoshitzky, S. R., Dye, J. M., Ramírez de Arellano, E., Negredo, A., Palacios, G., Kuhn, J. H., & Chandran, K. (2014). Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1. Virology, 468, 637-646. https://doi.org/10.1016/j.virol.2014.08.019