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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
eLife | 2015

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.

Pubmed ID: 26698106

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM093086
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI101436
  • Agency: NIGMS NIH HHS, United States
    Id: GM093086
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI088027
  • Agency: NIAID NIH HHS, United States
    Id: AI101436
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007288

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This is a list of tools and resources that we have found mentioned in this publication.


DataMonkey (tool)

RRID:SCR_010278

A free public server for comparative analysis of sequence alignments using state-of-the-art statistical models. This service is brought to you by the viral evolution group at the School Of Medicine of the University of California, San Diego.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

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TBLASTN (tool)

RRID:SCR_011822

Tool to search translated nucleotide databases using a protein query.

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Trinity (tool)

RRID:SCR_013048

Software for the efficient and robust de novo reconstruction of transcriptomes from RNA-seq data.

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Harmony (tool)

RRID:SCR_018809

Harmony high content imaging and analysis software. Used to quantify complex cellular phenotypes. Designed for PerkinElmer high content screening systems.

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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