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Virology. 2014 Nov;468-470:637-646. doi: 10.1016/j.virol.2014.08.019. Epub 2014 Oct 11.

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

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
2
Integrated Research Facility at Fort Detrick, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, United States.
3
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, United States.
4
National Center of Microbiology, Instituto de Salud Carlos III, 28220 Madrid, Spain.
5
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, United States. Electronic address: kartik.chandran@einstein.yu.edu.

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.

KEYWORDS:

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

PMID:
25310500
PMCID:
PMC4252868
DOI:
10.1016/j.virol.2014.08.019
[Indexed for MEDLINE]
Free PMC Article

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