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'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.

• Authors: 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
• Journal: Virology (Virology) Vol. 468-470 Pg. 637-646 (Nov 2014) ISSN: 1096-0341 [Electronic] United States
• PMID: 25310500 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Viral
• Carrier Proteins
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• NPC1 protein, human
• Niemann-Pick C1 Protein
• Receptors, Cell Surface
• Receptors, Virus
• Cysteine Proteases

Topics

• Animals
• Antibodies, Viral
• Carrier Proteins (genetics, metabolism)
• Cell Line
• Chlorocebus aethiops
• Cysteine Proteases (metabolism)
• Endosomes (enzymology)
• Fibroblasts (virology)
• Filoviridae (physiology)
• Humans
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins (genetics, metabolism)
• Microscopy, Electron, Transmission
• Niemann-Pick C1 Protein
• Protein Structure, Tertiary
• Receptors, Cell Surface
• Receptors, Virus
• Vero Cells
• Virus Internalization