@article {10.7554/eLife.11785, article_type = {journal}, title = {Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats}, author = {Ng, Melinda and Ndungo, Esther and Kaczmarek, Maria E and Herbert, Andrew S and Binger, Tabea and Kuehne, Ana I and Jangra, Rohit K and Hawkins, John A and Gifford, Robert J and Biswas, Rohan and Demogines, Ann and James, Rebekah M and Yu, Meng and Brummelkamp, Thijn R and Drosten, Christian and Wang, Lin-Fa and Kuhn, Jens H and Müller, Marcel A and Dye, John M and Sawyer, Sara L and Chandran, Kartik}, editor = {Neher, Richard A}, volume = 4, year = 2015, month = {dec}, pub_date = {2015-12-23}, pages = {e11785}, citation = {eLife 2015;4:e11785}, doi = {10.7554/eLife.11785}, url = {https://doi.org/10.7554/eLife.11785}, 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 (\textit{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 \textit{NPC1} concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in \textit{Eidolon helvum} cells. Our work identifies \textit{NPC1} as a genetic determinant of filovirus susceptibility in bats, and suggests that some \textit{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, viral receptor, Niemann-Pick C1, Virus-host co-evolution, Positive selection, NPC1, host range}, journal = {eLife}, issn = {2050-084X}, publisher = {eLife Sciences Publications, Ltd}, }