Filovirus Receptor NPC1 Contributes to Species-specific Patterns of Ebolavirus Susceptibility in Bats

Overview

Journal Elife

Specialty Biology

Date 2015 Dec 25

PMID 26698106

Citations 73

Authors

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 Muller

John M Dye

Sara L Sawyer

Kartik Chandran

Affiliations

Soon will be listed here.

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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