Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 23, 2015
- Source ID
- 10.7554/elife.11785
Entities
People
- Ana I. Kuehne
- Andrew S Herbert
- Ann Demogines
- Christian Drosten
- Esther Ndungo
- Jens H. Kuhn
- John A Hawkins
- John M Dye
- Kartik Chandran
- Lin-Fa Wang
- Marcel A Müller
- Maria E Kaczmarek
- Melinda Ng
- Meng Yu
- Rebekah M James
- Robert J Gifford
- Rohan Biswas
- Rohit K Jangra
- Sara L. Sawyer
- Tabea Binger
- Thijn Brummelkamp
Organizations
- Albert Einstein College of Medicine
- Defense Threat Reduction Agency
- Duke–NUS Medical School
- European Commission
- Federal Ministry of Research, Technology and Space
- NKI
- National Institutes of Health
- National Research Foundation
- United States Army Medical Research Institute of Infectious Diseases
- University of Bonn
- University of Colorado Boulder
- University of Glasgow
- University of Texas at Austin