Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats
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...
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doaj-a4ca56856f3e47a9ba72fff1209120bf2021-05-05T00:10:58ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.11785Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in batsMelinda Ng0Esther Ndungo1Maria E Kaczmarek2Andrew S Herbert3Tabea Binger4Ana I Kuehne5Rohit K Jangra6John A Hawkins7Robert J Gifford8Rohan Biswas9Ann Demogines10Rebekah M James11Meng Yu12Thijn R Brummelkamp13Christian Drosten14Lin-Fa Wang15Jens H Kuhn16https://orcid.org/0000-0002-7800-6045Marcel A Müller17John M Dye18Sara L Sawyer19Kartik Chandran20https://orcid.org/0000-0003-0232-7077Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Integrative Biology, University of Texas at Austin, Austin, United StatesUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United StatesInstitute of Virology, University of Bonn Medical Center, Bonn, GermanyUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesInstitute for Computational Engineering and Sciences, University of Texas at Austin, Austin, United StatesUniversity of Glasgow MRC Virology Unit, Glasgow, United KingdomDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United StatesUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United StatesProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, SingaporeNetherlands Cancer Institute, Plesmanlaan, The NetherlandsInstitute of Virology, University of Bonn Medical Center, Bonn, Germany; German Centre for Infectious Diseases Research, Bonn, GermanyProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, SingaporeIntegrated Research Facility at Fort Detrick, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, United StatesInstitute of Virology, University of Bonn Medical Center, Bonn, GermanyUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United StatesDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United States; BioFrontiers Institute, University of Colorado Boulder, Boulder, United States; Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United StatesDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United StatesBiological 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.https://elifesciences.org/articles/11785Ebola virusFilovirusviral receptorNiemann-Pick C1Virus-host co-evolutionPositive selection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats eLife Ebola virus Filovirus viral receptor Niemann-Pick C1 Virus-host co-evolution Positive selection |
author_facet |
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 |
author_sort |
Melinda Ng |
title |
Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats |
title_short |
Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats |
title_full |
Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats |
title_fullStr |
Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats |
title_full_unstemmed |
Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats |
title_sort |
filovirus receptor npc1 contributes to species-specific patterns of ebolavirus susceptibility in bats |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2015-12-01 |
description |
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. |
topic |
Ebola virus Filovirus viral receptor Niemann-Pick C1 Virus-host co-evolution Positive selection |
url |
https://elifesciences.org/articles/11785 |
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