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Elife. 2015 Dec 23;4. pii: e11785. doi: 10.7554/eLife.11785.

Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats.

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.
2
Department of Integrative Biology, University of Texas at Austin, Austin, United States.
3
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States.
4
Institute of Virology, University of Bonn Medical Center, Bonn, Germany.
5
Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, United States.
6
University of Glasgow MRC Virology Unit, Glasgow, United Kingdom.
7
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States.
8
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, , Singapore.
9
Netherlands Cancer Institute, Plesmanlaan, The Netherlands.
10
German Centre for Infectious Diseases Research, Bonn, Germany.
11
Integrated Research Facility at Fort Detrick, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, United States.
12
BioFrontiers Institute, University of Colorado Boulder, Boulder, United States.
13
Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States.

Abstract

Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature.

KEYWORDS:

Ebola virus; Filovirus; NPC1; Niemann-Pick C1; Positive selection; Virus-host co-evolution; bats; evolutionary biology; genomics; host range; infectious disease; microbiology; viral receptor; viruses

PMID:
26698106
PMCID:
PMC4709267
DOI:
10.7554/eLife.11785
[Indexed for MEDLINE]
Free PMC Article

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