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

Melinda Ng, Esther Ndungo, Maria E. Kaczmarek, Andrew S. Herbert, Tabea Binger, Ana I. Kuehne, Rohit K. Jangra, John A. Hawkins, Robert J. Gifford, Rohan Biswas, Ann Demogines, Rebekah M. James, Meng Yu, Thijn R. Brummelkamp, Christian Drosten, Lin Fa Wang, Jens H. Kuhn, Marcel A. Müller, John M. Dye, Sara L. SawyerKartik Chandran

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish (US)
Article numbere11785
JournaleLife
Volume4
Issue numberDECEMBER2015
DOIs
StatePublished - Dec 23 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    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., ... Chandran, K. (2015). Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats. eLife, 4(DECEMBER2015), [e11785]. https://doi.org/10.7554/eLife.11785