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

In order to assess transduction efficiency, we inoculated human (HEK-293T), non-human primate (Vero) and four fruit bat cell lines with VSVpp harboring filovirus GPs or VSV-G as control. First, we normalized the VSVpp for comparable transduction of HEK-293T cells and then used the particles for transduction of primate and bat cell lines (Fig 2A) . For Vero cells, the transduction mediated by filovirus GPs was roughly comparable to that measured for HEK-293T cells. However, the efficiency of entry mediated by the EBOV2014-GP was notably lower (~80%) than for the EBOV1976-GP, which is in line with previous results obtained for another African green monkey-derived cell line, COS-7 [47] . EpoNi/22.1 bat cells were also comparably susceptible to transduction by all GPs, although LLOV-GP-mediated entry was slightly increased (Fig 2A) . For the remaining three bat cell lines, marked differences in transduction by GPs representing different filovirus species were observed. Transduction of RoNi/7 and HypNi/1.1 cells by BDBV-and TAFV-GP bearing particles, respectively, was markedly reduced compared to transduction driven the other GPs (Fig 2A) . Even more profound differences were observed for EidNi/41 cells. The GPs of SUDV and LLOV facilitated robust transduction of the cells while both EBOV-GPs tested (1976 and 2014) as well as BDBV-GP failed to mediate entry into this cell line. TAFV-, RESTV-and MARV-GP-bearing VSVpp displayed intermediate transduction efficiency. Finally, when undiluted VSVpp were used for inoculation of EidNi/41 cells, we could detect low levels of luciferase activity, indicating that also EBOVand BDBV-GP are capable of mediating entry into cells of Eidolon helvum, albeit with low efficacy (Fig 2B) . In sum, the GPs of filovirus species differ widely in their ability to transduce target cells of certain reservoir species.