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. Sawyer; Kartik Chandran

doi:10.7554/eLife.11785

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

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

87 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 language	English (US)
Article number	e11785
Journal	eLife
Volume	4
Issue number	DECEMBER2015
DOIs	https://doi.org/10.7554/eLife.11785
State	Published - Dec 23 2015

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.11785

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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), Article e11785. https://doi.org/10.7554/eLife.11785

Ng, M, Ndungo, E, Kaczmarek, ME, Herbert, AS, Binger, T, Kuehne, AI, Jangra, RK, Hawkins, JA, Gifford, RJ, Biswas, R, Demogines, A, James, RM, Yu, M, Brummelkamp, TR, Drosten, C, Wang, LF, Kuhn, JH, Müller, MA, Dye, JM, Sawyer, SL & Chandran, K 2015, 'Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats', eLife, vol. 4, no. DECEMBER2015, e11785. https://doi.org/10.7554/eLife.11785

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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.",

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AU - Kuehne, Ana I.

AU - Jangra, Rohit K.

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AU - Demogines, Ann

AU - James, Rebekah M.

AU - Yu, Meng

AU - Brummelkamp, Thijn R.

AU - Drosten, Christian

AU - Wang, Lin Fa

AU - Kuhn, Jens H.

AU - Müller, Marcel A.

AU - Dye, John M.

AU - Sawyer, Sara L.

AU - Chandran, Kartik

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AB - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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