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Literature detail

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

Melinda Ng1 Esther Ndungo1 Maria E Kaczmarek2 Andrew S Herbert3 Tabea Binger4 Ana I Kuehne3 Rohit K Jangra1 John A Hawkins5 Robert J Gifford6 Rohan Biswas1 Ann Demogines7 Rebekah M James3 Meng Yu8 Thijn R Brummelkamp9 Christian Drosten4,10 Lin-Fa Wang8 Jens H Kuhn11 Marcel A Müller4 John M Dye3 Sara L Sawyer7,12,13 Kartik Chandran1
Affiliations 13 institutions
  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.
  2. Department of Integrative Biology, University of Texas at Austin, Austin, United States.
  3. United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, United States.
  4. Institute of Virology, University of Bonn Medical Center, Bonn, Germany.
  5. Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, United States.
  6. University of Glasgow MRC Virology Unit, Glasgow, United Kingdom.
  7. Department of Molecular Biosciences, University of Texas at Austin, Austin, United States.
  8. Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, , Singapore.
  9. Netherlands Cancer Institute, Plesmanlaan, The Netherlands.
  10. German Centre for Infectious Diseases Research, Bonn, Germany.
  11. Integrated Research Facility at Fort Detrick, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, United States.
  12. BioFrontiers Institute, University of Colorado Boulder, Boulder, United States.
  13. Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States.
PMID 26698106 2015 Elife eng epublish
PubMed DOI Browse context

Article

Publication summary

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.

bats Ebola virus evolutionary biology Filovirus genomics host range infectious disease microbiology Niemann-Pick C1 NPC1 Positive selection viral receptor Virus-host co-evolution viruses Host Specificity Virus Attachment Animals Cell Line

Structured evidence records

Evidence records

4 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.90
Key finding

Positive selection in bat NPC1 and a compensatory viral mutation demonstrate molecular co-evolution between filoviruses and their bat hosts, indicating mechanisms that shape filovirus host range.

Virus
EBOV
Location
Not specified
Supporting text

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. 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.

Genes or proteins
NPC1
Analysis methods
positive selection analysis
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.85
Key finding

Ebola virus failed to infect bat (Eidolon helvum) cells in vitro due to a species-specific NPC1 receptor variant that reduces viral entry affinity.

Virus
EBOV
Location
Not specified
Supporting text

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.

Method
infection assay; virus-receptor affinity assay
Experimental system
in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

A single amino acid change in bat NPC1 reduces Ebola virus binding, while a compensatory viral mutation restores interaction, illustrating co-adaptive molecular changes that shape host range.

Virus
EBOV
Host
Not specified
Location
Not specified
Supporting text

A single amino acid change in the filovirus receptor, NPC1, greatly reduces the affinity of EBOV-NPC1 interaction; 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.

Genes or proteins
NPC1
Receptors
NPC1
Mechanism types
receptor_binding; immune_escape; host_factor_interaction; transmission_fitness
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

A single amino acid change in bat NPC1 reduces the binding affinity between Ebola virus and the NPC1 receptor, restricting Ebola virus entry and infection in bat cells.

Virus
EBOV
Location
Not specified
Supporting text

Cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection, which could be explained by a single amino acid change in the filovirus receptor, NPC1, that greatly reduces the affinity of the EBOV–NPC1 interaction.

Receptors
NPC1