The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent

Hoffmann, Markus; González Hernández, Mariana; Berger, Elisabeth; Marzi, Andrea; Pöhlmann, Stefan

We employed rhabdoviral pseudotypes harboring GPs representing all filovirus species (EBOV, SUDV, BDBV, TAFV, RESTV, MARV, and LLOV) to study GP-mediated entry. Our results point towards pronounced differences in susceptibility of fruit bat cell lines to entry driven by filovirus GPs: Cells from the kidney of a Buettikofer's epauletted fruit bat (Epomops buettikoferi, EpoNi/22.1) were comparably susceptible to transduction mediated by all filovirus GPs tested. In contrast, cells from the Hammer-headed fruit bat (Hypsignathus monstrosus, HypNi/1.1) and the Egyptian fruit bat (Rousettus aegyptiacus, RoNi/7), displayed a reduced susceptibility for TAFV-GP-and BDBV-GP-driven pseudotype entry, respectively. The results obtained for transduction of RoNi/7, HypNi/1.1 and EpoNi/22.1 by EBOV-, SUDV-, RESTVand MARV-GP are in keeping with and expand previous studies [39, 42, 47] . More strikingly, we observed remarkable differences when GP-mediated transduction of a cell line was investigated that has been established from the kidney of a Straw-colored fruit bat (Eidolon helvum, EidNi/41). VSVpp decorated with either of the two EBOV-GPs or BDBV-GP failed to appreciably transduce these cells, while all other GPs mediated moderate (TAFV-, RESTV-, MARV-GP) to robust (SUDV-, LLOV-GP) transduction. During the revision of this manuscript Ng and colleagues reported inefficient EBOV-GP-driven entry into cells from the straw-colored fruit bat as compared to cells from other bats [73] . The inefficient entry was linked to a single amino acid polymorphism within the NPC1 molecule of this particular bat species [73] . These findings and the results of the present study indicate that filovirus entry into reservoir cells can be restricted at the stage of NPC1 usage. Moreover, they suggest that GPs representing different filovirus species might engage bat NPC1 orthologues slightly differently.