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

Ng, M. et al. (2015) Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats. eLife, 4, e11785. (doi:10.7554/eLife.11785) (PMID:26698106) (PMCID:PMC4709267)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gifford, Dr Robert
Authors: Ng, M., Ndungo, E., Kaczmarek, M. E., Herbert, A. S., Binger, T., Kuehne, A. I., Jangra, R. K., Hawkins, J. A., Gifford, R. J., Biswas, R., Demogines, A., James, R. M., Yu, M., Brummelkamp, T. R., Drosten, C., Wang, L.-F., Kuhn, J. H., Müller, M. A., Dye, J. M., Sawyer, S. L., and Chandran, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2015 Ng et al.
First Published:First published in eLife 4:e11785.
Publisher Policy:Reproduced under a Creative Commons License

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