OmniVira

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.
PMID26698106 DOI10.7554/eLife.11785 Year2015 Journal eLife Elife Languageeng Statusepublish

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.

bats 46 Ebola virus 18 evolutionary biology 3 Filovirus 15 genomics 39 host range 29 infectious disease 8 microbiology 5 Niemann-Pick C1 3 NPC1 2 Positive selection 8 viral receptor 3 Virus-host co-evolution 0 viruses 117 Host Specificity 132 Virus Attachment 55 Animals 1948 Cell Line 158 Chiroptera 371 Filoviridae 9 Membrane Glycoproteins 26 Receptors, Virus 204

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