eLife — 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


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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Bats and Rodents Shape Mammalian Retroviral Phylogeny

Bats and Rodents Shape Mammalian Retroviral Phylogeny
Jie Cui, Gilda Tachedjian & Lin-Fa Wang

Scientific Reports 5, Article number: 16561 (2015)

Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general.

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Emerging Infectious Disease: Filovirus RNA in Fruit Bats, China

Phylogenetic analysis showed that the Bt-DH04 strain is placed, together with LLOV, at basal position and intermediate between EBOV and MARV (Figure). It is divergent from all known filoviruses, with F1 sharing the highest nucleotide identities (46%–49%) to members of the genus Ebolavirus, followed by 44% to LLOV and <40% to MARV (Figure, panel A). The L gene is the most conserved region of filoviruses, and F2 of Bt-DH04 strain shared relatively closer 66%–68% nt identities with members of the genus Ebolavirus, followed by 64% with LLOV and ≈60% with MARV (Figure, panel B). This sequence diversity is likely the main factor for unsuccessful amplification of the full genome of Bt-DH04."

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